SMILES stringlengths 8 687 | MIE_Results unknown | AOP_ID listlengths 1 7 | AOP_Context listlengths 1 7 | Reasoning listlengths 1 6 | Overall_Assessment dict | Answer listlengths 1 3 |
|---|---|---|---|---|---|---|
CC(CC(=O)Nc1ccc(CCCNCC(O)c2ccc(O)c3[nH]c(=O)ccc23)cc1)CC(C)(C)C | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP levels and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations (both delayed and early), which promote ectopic cardiac activity and arr... | [
"cardiotoxicity"
] |
COc1ccc(CC(C)NCC(O)c2ccc(O)c(NC=O)c2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias through enhanced automaticity and triggered activity. Sustained arrhyt... | [
"cardiotoxicity"
] |
COc1ccc(C[C@@H](C)NC[C@H](O)c2ccc(O)c(NC=O)c2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, leading to increased intracellular cAMP and dysregulated calcium handling in cardiac myocytes. This triggers both delayed and early afterdepolarizations, which promote ectopic electrical activity and arrhythmias. Sustained cardiac arrhythmias result in... | [
"cardiotoxicity"
] |
Cc1ccc(CCC(C)(C)NCC(O)c2ccc(O)c3[nH]c(=O)ccc23)cc1.Cl | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through compromised ca... | [
"cardiotoxicity"
] |
O=C(O)COc1ccc(-c2ccc3c(c2)C[C@@H](NC[C@H](O)c2cccc(Cl)c2)CC3)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias through the AOP 554 pathway. The resulting electrophysiological distur... | [
"cardiotoxicity"
] |
COc1ccc(CN2CCN(c3ccc(CCNCC(O)c4ccc(O)c(CO)c4)cc3)CC2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP levels and calcium handling dysregulation in cardiac myocytes. This leads to the generation of early and delayed afterdepolarizations, which promote ectopic electrical ac... | [
"cardiotoxicity"
] |
OCc1cc([C@@H](O)CNCCc2ccc(NC[C@H](O)c3ccccc3)cc2)ccc1O | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through disrupted electrical c... | [
"cardiotoxicity"
] |
OCc1cc([C@@H](O)CNCCc2ccc(NC[C@@H](O)c3ccccc3)cc2)ccc1O | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, triggering a cascade of intracellular signaling events that increase cAMP levels and dysregulate cardiac calcium handling. This leads to the generation of afterdepolarizations and cardiac arrhythmias through the AOP 554 pathway, resulting in cardiot... | [
"cardiotoxicity"
] |
OCc1cc(C(O)CNCCc2ccc(NCC(O)c3ccccc3)cc2)ccc1O | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through compromised cardiac f... | [
"cardiotoxicity"
] |
CN(C)CCCN(CCNCCc1ccc(O)c2[nH]c(=O)sc12)C(=O)CCOCCc1ccccc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2), triggering a mechanistic cascade that increases intracellular cAMP and calcium handling abnormalities in cardiac myocytes. This leads to the generation of early and delayed afterdepolarizations, which serve as ectopic foci for arrhythmia initia... | [
"cardiotoxicity"
] |
CC(C)(Cc1ccccc1C(F)(F)F)NCC(O)c1cc(O)cc2c1OCC(=O)N2 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of early and delayed afterdepolarizations, which initiate cardiac arrhythmias. Sustained arrhythmias compromise c... | [
"cardiotoxicity"
] |
CC(C)(Cc1ccccc1)NCC(O)c1ccc(O)c2c1OCC(=O)N2 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias through the AOP 554 pathway. Sustained arrhythmias compromise cardiac... | [
"cardiotoxicity"
] |
C[C@H](CNc1cccc(-c2occc2C(=O)O)c1)NC[C@H](O)c1cccc(Cl)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to the generation of afterdepolarizations (both early and delayed), which disrupt normal cardiac electrical activity and preci... | [
"cardiotoxicity"
] |
C[C@H](Cc1c[nH]c2c(OS(=O)(=O)c3ccc(C(=O)O)cc3)cccc12)NC[C@H](O)c1cccc(NS(=O)(=O)c2cccs2)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP levels and calcium handling abnormalities in cardiac myocytes. This leads to increased early and delayed afterdepolarizations, which promote cardiac arrhythmias. Susta... | [
"cardiotoxicity"
] |
COc1ccc(CNCc2cccc(CCNC[C@H](O)c3ccc(O)c4[nH]c(=O)sc34)c2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), initiating a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of early and delayed afterdepolarizations, which promote cardiac arrhythmias through ectopic activity ... | [
"cardiotoxicity"
] |
C[C@H](Cc1cccc(CCNC(=O)c2ccc(N(C)C(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)cc2)c1)NC[C@H](O)c1ccc(O)c2[nH]c(=O)ccc12 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cyclic adenosine monophosphate (cAMP) levels in cardiac myocytes.",
... | {
"Summary": "The query compound activates the beta-2 adrenergic receptor (ADRB2), initiating a mechanistic cascade that increases intracellular cAMP and calcium signaling in cardiac myocytes. This dysregulation of calcium handling promotes both early and delayed afterdepolarizations, which serve as triggers for card... | [
"cardiotoxicity"
] |
C[C@@H](Cc1cccc(CCNC(=O)c2ccc(N(C)C(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)cc2)c1)NC[C@H](O)c1ccc(O)c2[nH]c(=O)ccc12 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The query compound activates the beta-2 adrenergic receptor (ADRB2), initiating a mechanistic cascade that increases intracellular cAMP levels in cardiac myocytes. This elevation in cAMP promotes excessive calcium handling through PKA-mediated phosphorylation of calcium regulatory proteins, generating b... | [
"cardiotoxicity"
] |
CCN(CC)CCN(CCNCCc1ccc(O)c2[nH]c(=O)sc12)C(=O)CCOCCc1ccc2ccccc2c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal electrical activity characterized by delayed and early afterdepolarizations, which precipitate cardiac arrhythmias... | [
"cardiotoxicity"
] |
CC(C)(Cc1ccc(C(F)(F)F)cc1)NCC(O)c1ccc(O)c2c1OCC(=O)N2 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors, initiating a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of early and delayed afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and re-entr... | [
"cardiotoxicity"
] |
CC(C)NC[C@H](O)COc1ccc(O)c(O)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and re-entry mechanisms.... | [
"cardiotoxicity"
] |
CC(C)NCC(O)c1ccc(N)c(C#N)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately causing cardiotoxicity through disrupted electrical condu... | [
"cardiotoxicity"
] |
CC(C)N(CC[C@H](c1ccccc1)c1cc(CCCNC(=O)CCCCCCCCCCNC[C@H](O)c2ccc(O)c(NS(C)(=O)=O)c2)ccc1O)C(C)C | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation. This leads to generation of afterdepolarizations and cardiac arrhythmias, which compromise cardiac function and cause cardiotoxicity thro... | [
"cardiotoxicity"
] |
Cn1c(=O)[nH]c2cccc(OC[C@@H](O)CNC(C)(C)Cc3ccc(Oc4ccc(C(N)=O)cn4)cc3)c21 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and re-entry mechanisms. ... | [
"cardiotoxicity"
] |
O=C(C(c1ccccc1)c1ccccc1)N1CCN(c2ccccn2)CC1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through comp... | [
"cardiotoxicity"
] |
Cl.O=C1COc2c(C(O)CNCCCc3cccc(F)c3)ccc(O)c2N1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP and calcium handling dysregulation in cardiac myocytes. This leads to the generation of early and delayed afterdepolarizations, which promote cardiac arrhythmias. Sust... | [
"cardiotoxicity"
] |
NCCCOc1ccc(Nc2ccc(CCNC[C@H](O)c3ccc(O)c4[nH]c(=O)ccc34)cc2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cyclic adenosine monophosphate (cAMP) levels in cardi... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2), triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of early and delayed afterdepolarizations, which initiate cardiac arrhythmias through abnormal electrical... | [
"cardiotoxicity"
] |
CN(Cc1ccccc1F)c1nc(-c2cccnc2)nc2ccccc12 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation. This leads to abnormal cardiac electrophysiology characterized by afterdepolarizations and arrhythmias, ultimately resulting in cardiotox... | [
"cardiotoxicity"
] |
C[C@H](CNc1ccc(CC(=O)NS(C)(=O)=O)cc1)NC[C@H](O)c1cccc(Cl)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of early and delayed afterdepolarizations, which initiate cardiac arrhythmias. Sustained arrhythmias compromise c... | [
"cardiotoxicity"
] |
O=c1[nH]c2c(O)ccc([C@@H](O)CNCCCOCCOCCc3cccc4ccccc34)c2s1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP levels and calcium dysregulation in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustai... | [
"cardiotoxicity"
] |
Cl.O=C1COc2c(C(O)CNCCCCc3ccccc3)ccc(O)c2N1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 adrenergic receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2), triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to increased afterdepolarizations (both delayed and early), which generate ectopic electrical activity and cardiac arrh... | [
"cardiotoxicity"
] |
Cl.O=c1ccc2c(C(O)CNCCCc3cccc(F)c3)ccc(O)c2[nH]1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2), triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through disrupted ele... | [
"cardiotoxicity"
] |
C[C@H](Cc1cccc(CC(=O)NCC2CCCCC2)c1)NC[C@H](O)c1ccc(O)c(NS(C)(=O)=O)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP levels and calcium dysregulation in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustai... | [
"cardiotoxicity"
] |
CN(C(=O)CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1)c1cccc(C(=O)Nc2cccc(CCNC[C@H](O)c3ccc(O)c4[nH]c(=O)ccc34)c2)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cyclic adenosine monophosphate (cAMP) levels in cardi... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, triggering a cascade of intracellular signaling that increases cAMP and calcium handling abnormalities in cardiac myocytes. This leads to the generation of early and delayed afterdepolarizations, which promote ectopic cardiac activity and arrhythmia... | [
"cardiotoxicity"
] |
Cc1ccc(C(=O)Nc2ccc(CC(C)NC[C@H](O)c3ccc(O)c4[nH]c(=O)ccc34)cc2)cc1N(C)C(=O)CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The query compound activates the beta-2 adrenergic receptor (ADRB2), initiating a mechanistic cascade that increases intracellular cAMP and calcium signaling in cardiac myocytes. This dysregulation promotes afterdepolarizations and cardiac arrhythmias through the established AOP 554 pathway. The resulti... | [
"cardiotoxicity"
] |
COc1ccc(CCNC[C@H](O)c2cc(O)cc(O)c2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through compromised ca... | [
"cardiotoxicity"
] |
COc1ccc(CCNC[C@@H](O)c2cc(O)cc(O)c2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, which compromise cardiac function and cause cardiotoxicity.",
"Pre... | [
"cardiotoxicity"
] |
CC(=O)O.NC(=O)NCc1cccc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(CO)c2)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevated cAMP activates... | {
"Summary": "The query compound activates the beta-2 adrenergic receptor (ADRB2), which initiates a mechanistic cascade leading to cardiotoxicity. ADRB2 activation increases intracellular cAMP levels in cardiac myocytes, enhancing calcium handling through PKA-mediated phosphorylation of calcium regulatory proteins. ... | [
"cardiotoxicity"
] |
COc1cccc(Nc2c(C(N)=O)ccc3c(C)cc(S(=O)(=O)c4cccc(C(=O)Nc5ccc(C#CCCCNC[C@@H](O)c6ccc(O)c7[nH]c(=O)ccc67)cc5)c4)cc23)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The query compound activates the beta-2 adrenergic receptor (ADRB2), triggering a well-established adverse outcome pathway that leads to cardiac arrhythmias. ADRB2 activation increases intracellular cAMP levels, which enhances calcium handling in cardiac myocytes through PKA-mediated phosphorylation of ... | [
"cardiotoxicity"
] |
NC(=O)CC(NC(=O)c1cccc(Br)c1)c1ccc(N2CCN(c3ccccn3)CC2)c([N+](=O)[O-])c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP levels and calcium dysregulation in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote ectopic activity and arrhyt... | [
"cardiotoxicity"
] |
COc1ccc(Nc2ccc(CCNC[C@H](O)c3ccc(O)c(CO)c3)cc2)cc1-c1ccccc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation. This leads to abnormal afterdepolarizations (both delayed and early), which promote cardiac arrhythmias through ectopic activity and re-e... | [
"cardiotoxicity"
] |
COc1ccc(Nc2ccc(CCNCC(O)c3ccc(O)c(CO)c3)cc2)cc1-c1ccccc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2), triggering a cascade of intracellular signaling events characterized by elevated cAMP and enhanced calcium handling in cardiac myocytes. This leads to increased afterdepolarizations (both delayed and early), which promote ectopic activity and a... | [
"cardiotoxicity"
] |
OCc1cc(C(O)CNCCc2ccc(Nc3cccc4ccccc34)cc2)ccc1O | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustained arrhythmic activity compr... | [
"cardiotoxicity"
] |
CCN(Cc1ccc(O)cc1Cl)C(=O)Cc1cccc(CC(C)(C)NC[C@H](O)c2ccc(O)c(NS(C)(=O)=O)c2)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), initiating a mechanistic cascade that increases intracellular cAMP levels in cardiac tissue. This elevation in cAMP enhances calcium handling through PKA-mediated phosphorylation of calcium regulatory proteins, leading to increased delayed a... | [
"cardiotoxicity"
] |
O=C(O)c1ccc(Oc2ccc3c(c2)C[C@@H](NC[C@H](O)c2cccc(Cl)c2)CC3)nc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, triggering a cascade of intracellular signaling events that increase cAMP levels and calcium dysregulation in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic... | [
"cardiotoxicity"
] |
CCOC(=O)S(=O)(=O)Oc1cccc2c(C[C@@H](C)NC[C@H](O)c3cccc(NS(=O)(=O)c4cccs4)c3)c[nH]c12 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, triggering a cascade of intracellular signaling events that increase cAMP and calcium handling dysregulation in cardiac myocytes. This leads to the generation of early and delayed afterdepolarizations, which promote cardiac arrhythmias. Sustained ar... | [
"cardiotoxicity"
] |
O=C(CCOCCc1ccccc1)NCCNCCc1ccc(O)c2nc(O)sc12 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2), triggering a cascade of intracellular signaling events characterized by increased cAMP production and calcium dysregulation. This leads to the generation of delayed and early afterdepolarizations in cardiac myocytes, which disrupt normal electr... | [
"cardiotoxicity"
] |
O=c1ccc2c(C(O)CNCCCc3ccccc3O)ccc(O)c2[nH]1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium signaling in cardiac myocytes. This dysregulation of calcium homeostasis promotes early and delayed afterdepolarizations, leading to cardiac arrhythmias. Sustained arrhythmi... | [
"cardiotoxicity"
] |
CC(C)(C)NC(CO)c1cc(F)c(N)c(S(=O)(=O)c2ccccc2)c1.Cl | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2), triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias through the AOP 554 pathway. Sustained arrhythmias compromise... | [
"cardiotoxicity"
] |
CCOc1ccc(Nc2ccc(CCNC[C@H](O)c3ccc(O)c4[nH]c(=O)ccc34)cc2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, triggering a cascade of intracellular signaling events that increase cAMP levels and calcium dysregulation in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustained arrh... | [
"cardiotoxicity"
] |
CC(C)(Cc1ccc(C(=O)O)cc1)NCC(O)c1ccc(O)c2c1OCC(=O)N2 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and re-entr... | [
"cardiotoxicity"
] |
COc1ccc(CC(C)(C)NC[C@@H](O)c2cc(O)cc3c2OCC(=O)N3)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through impaired electrical and mechan... | [
"cardiotoxicity"
] |
COc1ccc(CC(C)(C)NC[C@H](O)c2cc(O)cc3c2OCC(=O)N3)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through hemodynamic compromise... | [
"cardiotoxicity"
] |
COc1ccc(CC(C)(C)NCC(O)c2cc(O)cc3c2OCC(=O)N3)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, triggering a cascade of intracellular signaling events that increase cAMP levels and calcium handling dysregulation in cardiac myocytes. This leads to the generation of afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxi... | [
"cardiotoxicity"
] |
C[C@H](CNc1ccc(-c2nc(C(=O)O)co2)cc1)NC[C@H](O)c1cccc(Cl)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, triggering a cascade of intracellular signaling events that increase cAMP and calcium handling abnormalities in cardiac myocytes. This leads to the generation of early and delayed afterdepolarizations, which serve as triggers for cardiac arrhythmias... | [
"cardiotoxicity"
] |
O=C(O)c1cccc(-c2cccc(NCCNC[C@H](O)c3cccc(Cl)c3)c2)n1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), initiating a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to increased afterdepolarizations (both delayed and early), which promote cardiac arrhythmias through ectopic activi... | [
"cardiotoxicity"
] |
O=c1[nH]c2c(O)ccc([C@@H](O)CNCCCOCCNCCc3cccc(Cl)c3)c2s1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, triggering a cascade of intracellular signaling events that increase cAMP levels and calcium dysregulation in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic... | [
"cardiotoxicity"
] |
O=C(c1ccc(OC2CCN(Cc3ccc(C(F)(F)F)cc3)CC2)cc1)N1CCCCC1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through compromised cardiac f... | [
"cardiotoxicity"
] |
CN(CCCC(=O)Nc1ccc(CNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)cc1)C(=O)CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and re-entr... | [
"cardiotoxicity"
] |
COC(=O)c1ccc(NC(=O)COc2ccc(S(=O)(=O)N3CCCCC3)cc2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation. This leads to abnormal afterdepolarizations and cardiac arrhythmias through the AOP 554 pathway. Sustained arrhythmic activity compromise... | [
"cardiotoxicity"
] |
CC[C@H](Cc1ccc2[nH]c(C(=O)NCc3c(OC)cccc3OC)cc2c1)NC[C@H](O)c1ccc(O)c(CO)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation. This leads to abnormal cardiac electrical activity through afterdepolarizations, ultimately manifesting as cardiac arrhythmias and... | [
"cardiotoxicity"
] |
CN(C(=O)CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1)c1ccc(CNC(=O)Cc2cccc(CNC[C@H](O)c3ccc(O)c4[nH]c(=O)ccc34)c2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2) in cardiac tissue, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation. This leads to generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and r... | [
"cardiotoxicity"
] |
CCn1c(C(=O)NCc2c(OC)cccc2OC)cc2cc(C[C@@H](C)NC[C@H](O)c3ccc(O)c(CO)c3)ccc21 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling that increases cAMP levels and dysregulates cardiac calcium handling. This leads to the generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustained arrhyt... | [
"cardiotoxicity"
] |
CC(C)(Cc1ccc(Br)cc1)NCC(O)c1cc(O)cc2c1OCC(=O)N2 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through disrupted elec... | [
"cardiotoxicity"
] |
OCc1cc(C(O)CNCCc2ccc(NCC(O)c3ccc(-c4ccccc4)cc3)cc2)ccc1O | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, initiating a mechanistic cascade that increases intracellular cAMP and calcium handling dysregulation in cardiac myocytes. This leads to generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustained arrhythmic ac... | [
"cardiotoxicity"
] |
O=C(CCCCCn1c(=O)[nH]c2ccsc2c1=O)NCc1ccc(F)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium handling abnormalities. This leads to the generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustained arrhythmias... | [
"cardiotoxicity"
] |
CC(=O)O.OCCOCCCCCCNC[C@H](O)c1ccc(O)c(CO)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, which compromise cardiac function and cause cardiot... | [
"cardiotoxicity"
] |
CC1=NCCc2c1[nH]c1ccccc21 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately causing cardiotoxicity through compromised cardiac functi... | [
"cardiotoxicity"
] |
O=C(Cc1cccc(CCNC[C@H](O)c2ccc(O)c(CO)c2)c1)NCc1ccccc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to enhanced afterdepolarizations (both delayed and early), promoting ectopic activity and arrhythmias. Sustained cardiac arrhyt... | [
"cardiotoxicity"
] |
CCOc1ccc2nc(NC(=O)CSc3nc4cccnc4n3C)sc2c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium handling dysregulation. This leads to the generation of delayed and early afterdepolarizations, which disrupt normal cardiac electrophysiology and preci... | [
"cardiotoxicity"
] |
CC(C)(CCc1ccc(Cl)cc1)NC[C@H](O)c1ccc(O)c2[nH]c(=O)ccc12.Cl | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, initiating a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and re-entr... | [
"cardiotoxicity"
] |
CC(C)(CCc1ccc(Cl)cc1)NCC(O)c1ccc(O)c2[nH]c(=O)ccc12.Cl | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and re-entry mechanisms.... | [
"cardiotoxicity"
] |
O=C(Nc1cccc(-c2nc3ncccc3o2)c1)c1sc2cc(Cl)ccc2c1Cl | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, initiating a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and re-entr... | [
"cardiotoxicity"
] |
CN(CCCC(=O)Nc1ccc(CCNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)cc1)C(=O)CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, triggering a cascade of intracellular signaling events characterized by elevated cAMP and enhanced calcium handling in cardiac myocytes. This dysregulation of calcium dynamics promotes the generation of delayed and early afterdepolarizations, which ... | [
"cardiotoxicity"
] |
CCCCN(CCCC)c1nc2ccccc2nc1NS(=O)(=O)c1ccc(NC(C)=O)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium handling abnormalities. This leads to delayed and early afterdepolarizations that generate ectopic electrical activity and arrhythmias. Sustained arrhyt... | [
"cardiotoxicity"
] |
O=c1[nH]c2c(O)ccc(CCNCCc3cccc(CN[C@H]4C[C@@H]4c4ccccc4)c3)c2s1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor, triggering a cascade of intracellular signaling events that increase cAMP levels and dysregulate calcium homeostasis in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote ectopic cardiac activity ... | [
"cardiotoxicity"
] |
O=S(=O)(CCCOCCc1ccccc1)CCNCCc1ccc(O)c2nc(O)sc12 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), initiating a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to delayed and early afterdepolarizations, triggering cardiac arrhythmias through abnormal electrical activity. Sust... | [
"cardiotoxicity"
] |
CC(C)(C)NC[C@@H](O)COc1ccccc1-c1ccccc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustained arrhythmias compromise cardiac functio... | [
"cardiotoxicity"
] |
CC(C)(C)NC(CO)c1cc(Br)c(N)c(C#N)c1.Cl | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP levels and calcium handling dysregulation in cardiac myocytes. This leads to the generation of abnormal afterdepolarizations (early and delayed) that disrupt normal ca... | [
"cardiotoxicity"
] |
COc1cc(NC(=O)c2cccc(N(C)C(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)c2)c(C)cc1CNC[C@H](O)c1ccc(O)c2[nH]c(=O)ccc12 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation. This leads to abnormal cardiac electrical activity manifesting as delayed and early afterdepolarizations, ultimately causing cardiac arrh... | [
"cardiotoxicity"
] |
CC(C)(CC(c1ccccc1)c1ccccc1)NCC(O)c1ccc(O)c2[nH]c(=O)ccc12 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias through enhanced automaticity and triggered activity. The resu... | [
"cardiotoxicity"
] |
CC(C)(CC(c1ccccc1)c1ccccc1)NC[C@H](O)c1ccc(O)c2[nH]c(=O)ccc12 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote ectopic cardiac activity and arrhythmias. Th... | [
"cardiotoxicity"
] |
CC(=O)O.CCNC(=O)NCc1cccc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(CO)c2)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevated cAMP activates... | {
"Summary": "The query compound activates the beta-2 adrenergic receptor (ADRB2), which initiates a mechanistic cascade leading to increased intracellular cAMP and calcium dysregulation in cardiac myocytes. This dysregulation promotes delayed and early afterdepolarizations, triggering cardiac arrhythmias. Sustained ... | [
"cardiotoxicity"
] |
CCCCC(=O)Nc1ccc(C(=O)N2CCCC(C(=O)OCC)C2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2), initiating a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of early and delayed afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and... | [
"cardiotoxicity"
] |
O=C(C[n+]1cccc(NC(=O)c2ccccc2)c1)c1ccc(NC(=O)c2ccccc2)cc1.[Br-] | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation. This leads to the generation of afterdepolarizations and cardiac arrhythmias through the AOP 554 pathway. The resulting electrical instab... | [
"cardiotoxicity"
] |
COc1ccc(CCNCC(O)c2ccc(O)c3c2OCC(=O)N3)cc1.Cl | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling events that increase cAMP and calcium handling dysregulation. This leads to the generation of delayed and early afterdepolarizations, which disrupt normal cardiac electrophysiology and... | [
"cardiotoxicity"
] |
CC(=O)N(Cc1ccccc1O[11CH3])c1cnccc1Oc1ccccc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The query compound activates the beta-2 adrenergic receptor (ADRB2), which initiates a mechanistic cascade leading to increased intracellular cAMP levels in cardiac myocytes. This elevation in cAMP promotes excessive calcium handling through PKA-mediated phosphorylation of calcium regulatory proteins, r... | [
"cardiotoxicity"
] |
CCCCCCNC(=O)Nc1ccc(S(=O)(=O)Nc2cccc(-c3cccc(CC4NCCc5cc(O)c(O)cc54)c3)c2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The query compound activates the beta-2 adrenergic receptor (ADRB2), which initiates a mechanistic cascade leading to cardiotoxicity. ADRB2 activation increases intracellular cAMP levels, promoting excessive calcium mobilization in cardiac myocytes. This dysregulation of calcium handling generates delay... | [
"cardiotoxicity"
] |
OCc1cc(C(O)CNCCc2ccc(NCC(O)c3ccc(Cl)cc3)cc2)ccc1O | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP levels and dysregulate calcium homeostasis in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote cardiac arrhythmi... | [
"cardiotoxicity"
] |
CC(C)(Cc1cccc(C(F)(F)F)c1)NCC(O)c1ccc(O)c(CO)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation in cardiac myocytes. This leads to increased afterdepolarizations (both delayed and early), which promote cardiac arrhythmias through ectopic activity ... | [
"cardiotoxicity"
] |
Nc1nc2c(c(N3CCNCC3)n1)CCC1=C2[C@@H]2CCCC[C@@H]2O1 | {
"ADRB2": "Activation",
"AT1R": "Activation",
"GR": "Activation"
} | [
"Aop:554",
"Aop:384",
"Aop:318"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n",
"\nAop:384\nTitle: Hyperactivation of ACE/Ang-II/AT1R axis... | [
{
"MIE": "ADRB2 Activation",
"Reasoning_Steps": [
"Step 1: Activation of beta-2 adrenergic receptor (ADRB2) leads to increased intracellular cAMP levels through G-protein coupled signaling cascades.",
"Step 2: Elevated cAMP promotes increased delayed and early afterdepolarizations in cardiac myo... | {
"Summary": "The query compound activates three critical receptors (ADRB2, AT1R, and GR) that trigger distinct mechanistic pathways leading to multi-organ toxicity. ADRB2 activation disrupts cardiac electrical homeostasis through cAMP-mediated afterdepolarizations, causing arrhythmias. AT1R activation hyperactivates... | [
"kidney toxicity",
"cardiotoxicity",
"liver toxicity"
] |
CN1CCN(c2ccc(-c3cccc(CN4CCOCC4)c3)cc2NC(=O)c2c[nH]c(=O)cc2C(F)(F)F)CC1 | {
"ADRB2": "Activation",
"AT1R": "Activation"
} | [
"Aop:554",
"Aop:384"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n",
"\nAop:384\nTitle: Hyperactivation of ACE/Ang-II/AT1R axis... | [
{
"MIE": "ADRB2 Activation",
"Reasoning_Steps": [
"Step 1: Activation of beta-2 adrenergic receptor (ADRB2) triggers increased intracellular cAMP levels through G-protein coupled signaling cascades.",
"Step 2: Elevated cAMP enhances calcium handling and increases the probability of delayed and e... | {
"Summary": "The query compound activates both ADRB2 and AT1R, triggering two distinct mechanistic pathways leading to organ toxicity. ADRB2 activation increases intracellular cAMP, promoting cardiac afterdepolarizations and arrhythmias that compromise cardiac function. Simultaneously, AT1R activation hyperactivates... | [
"kidney toxicity",
"cardiotoxicity"
] |
C[C@H](Cc1c[nH]c2c(OS(C)(=O)=O)cccc12)NC[C@H](O)c1cccc(NS(=O)(=O)c2cccc(N)c2)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias through the AOP 554 pathway, ultimately resulting in... | [
"cardiotoxicity"
] |
Nc1ccc([C@@H](O)CNCCc2ccc(-c3ccc(C(=O)O)c(OC4CCCCC4)c3)cc2)cn1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, initiating a mechanistic cascade that increases intracellular cAMP and calcium handling dysregulation in cardiac myocytes. This leads to generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias through ectopic activity an... | [
"cardiotoxicity"
] |
C[C@H](Cc1cn2c3c(cccc13)OCCC2)NC[C@H](O)c1cccc(NS(=O)(=O)c2cccs2)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors (ADRB2) in cardiac tissue, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation. This leads to abnormal cardiac electrophysiology characterized by delayed and early afterdepolarizations, ultimately manifesting as ... | [
"cardiotoxicity"
] |
C[C@H](CNc1cccc(-c2ncccc2C(=O)O)c1)NC[C@H](O)c1cccc(Cl)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), initiating a mechanistic cascade that increases intracellular cAMP levels in cardiac myocytes. This elevation in cAMP promotes excessive calcium handling through PKA-mediated phosphorylation of calcium regulatory proteins, generating both de... | [
"cardiotoxicity"
] |
O=c1ccc2c(C(O)CNCCCc3ccc4ccccc4c3)ccc(O)c2[nH]1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias through the AOP 554 pathway. Sustained arrhythmias c... | [
"cardiotoxicity"
] |
O=C(Nc1ccc(S(=O)(=O)N2CCCCC2c2cccnc2)cc1)c1c(F)cccc1F | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through compromised cardiac f... | [
"cardiotoxicity"
] |
CSc1ccc(CN2CCC(Oc3ccc(C(=O)N4CCCC4)cc3)CC2)cc1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates beta-2 adrenergic receptors on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium handling abnormalities. This leads to increased early and delayed afterdepolarizations, which promote cardiac arrhythmias. Sustained arrhythmias comprom... | [
"cardiotoxicity"
] |
CC#CCNc1cccc([C@@H](O)CN[C@H](C)Cc2c[nH]c3c(OS(C)(=O)=O)cccc23)c1 | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of ADRB2 (Beta-2 Adrenergic Receptor)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevated intracellular cAMP levels in cardiac myocytes.",
"Step 2: Elevate... | {
"Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling events that increase cAMP levels and calcium dysregulation in cardiac myocytes. This leads to the generation of early and delayed afterdepolarizations, which promote ectopic electrical activity... | [
"cardiotoxicity"
] |
COc1cccc(CCNCC(O)c2ccc(O)c3c2OCC(=O)N3)c1.Cl | {
"ADRB2": "Activation"
} | [
"Aop:554"
] | [
"\nAop:554\nTitle: β-adrenergic receptor agonists leading to arrhythmias.\nAOP: Activation, beta-2 adrenergic receptor --> Increased Intracellular cAMP Levels --> Increased the delayed and early afterdepolarizations --> Occurrence, cardiac arrhythmia\n"
] | [
{
"MIE": "Activation of beta-2 adrenergic receptor (ADRB2)",
"Reasoning_Steps": [
"Step 1: ADRB2 activation by the compound triggers G-protein coupled receptor signaling, leading to increased adenylyl cyclase activity and elevation of intracellular cAMP levels in cardiac myocytes.",
"Step 2: Ele... | {
"Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through compromised cardiac f... | [
"cardiotoxicity"
] |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.