Datasets:

dmis-lab
/

ToxReason

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
COC(=O)[C@@H]1CCCN1C(=O)[C@@H](Cc1ccccc1)N(C)C(=O)[C@H](C)NC(=O)[C@@H](NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](OC(=O)[C@@H](OC(=O)[C@H](C(C)C)N(C)C)C(C)C)C(C)C)[C@@H](C)O	{ "ACE": "Activation" }	[ "Aop:384" ]	[ "\nAop:384\nTitle: Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease\nAOP: Hyperactivation of ACE/Ang-II/AT1R axis --> Increased Angiotensin II --> Increased Ang II type 1 receptor (AT1R) --> Increase, Reactive oxygen species --> Increased Sodium-sensitive hypertension --> Chronic kidney dis...	[ { "MIE": "ACE Activation", "Reasoning_Steps": [ "Step 1: ACE activation catalyzes the conversion of Angiotensin I to Angiotensin II, leading to increased circulating and tissue Angiotensin II levels.", "Step 2: Elevated Angiotensin II binds to AT1R receptors on vascular smooth muscle cells and r...	{ "Summary": "The query compound activates ACE, leading to hyperactivation of the ACE/Angiotensin II/AT1R axis. This cascade increases Angiotensin II production, which binds AT1R receptors and triggers ROS generation in renal tissue. The resulting oxidative stress, combined with sodium-sensitive hypertension from enh...	[ "kidney toxicity" ]
C/C=C1\NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](COS(=O)(=O)[O-])OC)C(C)C)[C@@H](C)OC(=O)[C@H]([C@H](C)CC)NC(=O)[C@H](Cc2ccccc2)N(C)C(=O)[C@H](Cc2ccccc2)N2C(=O)[C@H](CC[C@H]2O)NC1=O.[Na+]	{ "ACE": "Activation" }	[ "Aop:384" ]	[ "\nAop:384\nTitle: Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease\nAOP: Hyperactivation of ACE/Ang-II/AT1R axis --> Increased Angiotensin II --> Increased Ang II type 1 receptor (AT1R) --> Increase, Reactive oxygen species --> Increased Sodium-sensitive hypertension --> Chronic kidney dis...	[ { "MIE": "ACE Activation", "Reasoning_Steps": [ "Step 1: ACE activation catalyzes the conversion of Angiotensin I to Angiotensin II, leading to increased circulating and tissue Angiotensin II levels.", "Step 2: Elevated Angiotensin II binds to and activates AT1R (Angiotensin II type 1 receptor) ...	{ "Summary": "The query compound activates ACE, leading to hyperactivation of the ACE/Angiotensin II/AT1R axis. This cascade increases Angiotensin II production, which overstimulates AT1R signaling and generates excessive reactive oxygen species in renal tissue. The resulting oxidative stress damages the glomerular f...	[ "kidney toxicity" ]
CCS(=O)(=O)n1c2c(c3cc(C(=O)N4CCC(C)CC4)ccc31)CN(C1CCOCC1)CC2	{ "ACE": "Activation", "AT1R": "Activation", "KCNH2": "Inhibition" }	[ "Aop:384", "Aop:555" ]	[ "\nAop:384\nTitle: Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease\nAOP: Hyperactivation of ACE/Ang-II/AT1R axis --> Increased Angiotensin II --> Increased Ang II type 1 receptor (AT1R) --> Increase, Reactive oxygen species --> Increased Sodium-sensitive hypertension --> Chronic kidney dis...	[ { "MIE": "ACE Activation", "Reasoning_Steps": [ "Step 1: ACE activation increases conversion of angiotensin I to angiotensin II, elevating circulating and tissue Ang-II levels.", "Step 2: Elevated Ang-II binds to AT1R, triggering downstream signaling that increases reactive oxygen species (ROS) ...	{ "Summary": "The compound activates both ACE and AT1R, hyperactivating the renin-angiotensin system and triggering a cascade of ROS-mediated kidney injury through chronic glomerulosclerosis and tubulointerstitial fibrosis, leading to chronic kidney disease. Simultaneously, KCNH2 inhibition impairs cardiac repolariza...	[ "kidney toxicity", "cardiotoxicity" ]
Cc1ccc(C(=O)Nc2ccc(CNC[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 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 the generation of early and delayed afterdepolarizations, which initiate ectopic electrical activity and c...	[ "cardiotoxicity" ]
CN(CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1)C(=O)c1ccc(CNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)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 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" ]
O=c1ccc2c(C(CO)NCCCCCCOCCCCc3ccccc3)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 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)CNCCCc3ccc(C(F)(F)F)cc3)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 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)CNCCC(c3ccccc3)c3ccccc3)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 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" ]
CC(C)(C)OC(=O)NCCOc1ccc(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 ADRB2 (β-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: Elevated c...	{ "Summary": "The compound activates β-2 adrenergic receptors (ADRB2) in cardiac tissue, triggering a mechanistic cascade that increases intracellular cAMP and calcium handling abnormalities. This leads to early and delayed afterdepolarizations that promote cardiac arrhythmias. Sustained arrhythmias compromise cardia...	[ "cardiotoxicity" ]
CC(=O)O.CNS(=O)(=O)c1cccc(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 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 and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias through the established AOP 554 pathway. The resulting arr...	[ "cardiotoxicity" ]
COc1ccccc1CNC(=O)Cc1cccc(C[C@@H](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 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" ]
CCN(CC)C(=O)COc1cccc2c(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 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 altered electrophysiology. Sustained arrhythmic activity comp...	[ "cardiotoxicity" ]
CCN(CC)CCN(CCNCCc1ccc(O)c2[nH]c(=O)sc12)C(=O)CCOCCc1cccc(F)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 on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP and calcium dysregulation. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately compromising cardiac function and causing cardiotoxicity....	[ "cardiotoxicity" ]
CC(=O)NCc1cccc(OC[C@@H](O)CNCCc2ccc(NC(=O)Nc3ccccc3)cc2)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, 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. Sustained arrhythmic activity impai...	[ "cardiotoxicity" ]
CN1C[C@H](C(=O)N[C@]2(C)O[C@@]3(O)[C@@H]4CCCN4C(=O)[C@H](Cc4ccccc4)N3C2=O)C[C@@H]2c3cccc4[nH]cc(c34)C[C@H]21.CS(=O)(=O)O	{ "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. The resulting electroph...	[ "cardiotoxicity" ]
O=C(NC1(Cc2ccc(O)cc2)CCCCC1)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 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" ]
Cc1cc(CNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)ccc1NC(=O)CCCCN(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 cyclic adenosine monophosphate (cAMP) levels in cardi...	{ "Summary": "The compound activates beta-2 adrenergic receptors, triggering a cascade of intracellular signaling that increases cAMP levels and calcium handling dysregulation in cardiac myocytes. This leads to abnormal cardiac electrical activity characterized by afterdepolarizations, ultimately resulting in arrhyth...	[ "cardiotoxicity" ]
CC(C)N(CC[C@H](c1ccccc1)c1cc(CCCCOc2ccc(CCNC[C@H](O)c3ccc(O)c(NS(C)(=O)=O)c3)cc2)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 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 dysregulation. This leads to abnormal cardiac electrophysiology characterized by afterdepolarizations and arrhythmias. Sustained arrhythmic activity com...	[ "cardiotoxicity" ]
COc1ccccc1OCCNC[C@H](O)c1ccc(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 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 signaling in cardiac myocytes. This leads to the generation of early and delayed afterdepolarizations, which promote cardiac arrhythmias. Sustained arrhythmias compr...	[ "cardiotoxicity" ]
COc1ccccc1OCCNC[C@@H](O)c1ccc(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 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 leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through impaired cardiac function ...	[ "cardiotoxicity" ]
COC(=O)c1cccc(-c2cccc(NCCNC[C@H](O)c3cccc(Cl)c3)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 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" ]
C[C@H](Cc1c[nH]c2ccccc12)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 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. Sustained arrhythmias compromise ca...	[ "cardiotoxicity" ]
CC(Cc1c[nH]c2ccccc12)NCC(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 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. The resulting electroph...	[ "cardiotoxicity" ]
C[C@H](Cc1c[nH]c2ccccc12)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, initiating a mechanistic cascade that increases intracellular cAMP and calcium signaling in cardiac myocytes. This dysregulation promotes afterdepolarizations and cardiac arrhythmias, ultimately compromising cardiac electrical stability and contractile...	[ "cardiotoxicity" ]
CN(C)c1ccc(-c2noc(C3CCN(S(=O)(=O)c4cccc(Cl)c4)CC3)n2)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 disrupt normal cardiac electrical activity, resulting in arrhythmias a...	[ "cardiotoxicity" ]
CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n(C2CCCC2)c1=O	{ "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 disrupt normal cardiac electrical activity, resulting in arrhythmias a...	[ "cardiotoxicity" ]
CC(CCc1ccccc1Cl)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 levels and calcium dysregulation in cardiac myocytes. This leads to increased afterdepolarizations (both delayed and early), which promote ectopic cardiac activity and arrhythmias. Sus...	[ "cardiotoxicity" ]
Cc1cccc(CCCNCC(O)c2ccc(O)c3[nH]c(=O)ccc23)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 mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately causing cardiotoxicity through impaired electrical conduct...	[ "cardiotoxicity" ]
NS(=O)(=O)c1cccc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(NC=O)c2)c1.O=C(O)/C=C/C(=O)O	{ "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. The resulting electroph...	[ "cardiotoxicity" ]
CN(Cc1ccccc1)S(=O)(=O)c1ccc(NS(=O)(=O)Cc2ccccc2)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 handling abnormalities. This leads to afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through compromised cardiac f...	[ "cardiotoxicity" ]
CN(CCOCCCNC[C@H](O)c1ccc(O)c2[nH]c(=O)sc12)CCc1ccccc1	{ "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 disrupt normal cardiac electrical activity ...	[ "cardiotoxicity" ]
CC(C)(CCc1ccccc1Cl)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 levels and calcium dysregulation in cardiac myocytes. This leads to generation of delayed and early afterdepolarizations, which disrupt normal cardiac electrical activity and cause arr...	[ "cardiotoxicity" ]
C[C@H](Cc1cccc(CC(=O)NC23CC4CC(CC(C4)C2)C3)c1)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 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(CCCCC(=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 cyclic adenosine monophosphate (cAMP) levels in cardi...	{ "Summary": "The compound activates the beta-2 adrenergic receptor, initiating a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to delayed and early afterdepolarizations, which promote abnormal cardiac electrical activity and arrhythmias. The resulting...	[ "cardiotoxicity" ]
NC(=O)CC(NC(=O)Cc1ccc(Cl)cc1)c1ccc(NCCCN2CCCC2=O)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 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 e...	[ "cardiotoxicity" ]
CC(C)(Cc1ccc(NC(=O)CCCNCCCS(=O)(=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 (ADRB2) on cardiac myocytes, triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation. This leads to generation of afterdepolarizations (both delayed and early types) that promote ectopic cardiac activity and ...	[ "cardiotoxicity" ]
CC(=O)c1cccc(S(=O)(=O)N2CCCC(c3nc(-c4ccc(C)o4)no3)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 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 abnormal afterdepolarizations and cardiac arrhythmias through the AOP 554 pathway, ultimately resul...	[ "cardiotoxicity" ]
CS(=O)(=O)Nc1cc([C@@H](O)CNCC2CCN(S(=O)(=O)c3ccc(-n4ccc5c(C(=O)O)cccc54)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 elevated intracellular cAMP levels in cardiac myocytes.", "Step 2: Elevate...	{ "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 enhanced early and delayed afterdepolarizations, promoting ectopic electrical activity and arrhythmias. Sustained...	[ "cardiotoxicity" ]
CC(C)(Cc1cccc(C(F)(F)F)c1)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 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), initiating a mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to increased early and delayed afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and re-...	[ "cardiotoxicity" ]
C[C@H](Cc1cccc(CC(=O)NCc2ccc(Cl)c(Cl)c2)c1)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 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 handling dysregulation in cardiac myocytes. This leads to increased early and delayed afterdepolarizations, promoting ectopic electrical activity and cardiac arrhythmias. Th...	[ "cardiotoxicity" ]
CC(=O)O.OCc1cc([C@@H](O)CNCCCCCCOCCOCc2cccc3ccccc23)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 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 delayed and early afterdepolarizations, which are abnormal electrical activities ...	[ "cardiotoxicity" ]
COc1cc2nc(N3CCNCC3)nc(N)c2cc1OC	{ "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, 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. Sustained arrhythmias compromise cardiac...	[ "cardiotoxicity" ]
COc1cc(CCCNCC(O)c2ccc(O)c3c2OCC(=O)N3)cc(OC)c1OC.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 through enhanced automaticity and triggered activity. The resu...	[ "cardiotoxicity" ]
Cc1ccc(C(=O)NCc2cccc(CC(C)NC[C@H](O)c3ccc(O)c4[nH]c(=O)ccc34)c2)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 elevated intracellular cAMP levels in cardiac myocytes.", "Step 2: Elevate...	{ "Summary": "The query compound activates the beta-2 adrenergic receptor, initiating a mechanistic cascade that increases intracellular cAMP and calcium signaling in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which trigger ectopic cardiac activity and arrhythmias. The r...	[ "cardiotoxicity" ]
CC(C)NCC(O)COc1cccc2ccccc12	{ "ADRB2": "Activation", "AT1R": "Activation", "KCNH2": "Inhibition", "SCN5A": "Inhibition" }	[ "Aop:554", "Aop:384", "Aop:555", "Aop:553" ]	[ "\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 β-2 adrenergic receptor increases intracellular cAMP levels, enhancing cardiac excitability and automaticity.", "Step 2: Elevated cAMP promotes delayed and early afterdepolarizations, creating ectopic firing foci in cardiac...	{ "Summary": "The compound exhibits multiple cardiotoxic mechanisms through ADRB2 activation and dual potassium/sodium channel inhibition. ADRB2 activation increases intracellular cAMP, promoting afterdepolarizations and arrhythmias. KCNH2 inhibition prolongs QT interval and facilitates early afterdepolarizations, wh...	[ "kidney toxicity", "cardiotoxicity" ]
O=S(=O)(c1cc(C(F)(F)F)ccc1Cl)N1CCN(CC(O)COCC2CCCO2)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 electrical activity characterized by delayed and early afterdepolarizations, which precipitate cardiac arrhythmias...	[ "cardiotoxicity" ]
Cc1cc(NC(=O)Cc2cccc(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 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 levels in cardiac tissue. This elevation in cAMP enhances calcium handling through PKA-mediated phosphorylation of calcium regulatory proteins, promoting both delayed a...	[ "cardiotoxicity" ]
CN(C(=O)CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1)c1cccc(C(=O)Nc2ccc(CNC[C@H](O)c3ccc(O)c4[nH]c(=O)ccc34)cc2)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 (ADRB2) on cardiac myocytes, triggering a cascade of intracellular signaling events that increase cAMP levels and calcium dysregulation. This leads to the generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustained...	[ "cardiotoxicity" ]
COc1cccc(CCC(C)(C)NCC(O)c2ccc(O)c3[nH]c(=O)ccc23)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 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" ]
COc1ccc(CNC(=O)Cc2ccc(N(C)C(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)cc2)cc1CC(C)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 and calcium dysregulation in cardiac myocytes. This leads to afterdepolarizations and cardiac arrhythmias, ultimately causing cardiotoxicity through disrupted electrical conduction and...	[ "cardiotoxicity" ]
CC(=O)O.O=S(=O)(c1cccc(CCCCOCCCCCCNC[C@H](O)c2ccc(O)c(CO)c2)c1)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 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 abnormal afterdepolarizations and cardiac arrhythmias through the AOP 554 pathway. The resulting el...	[ "cardiotoxicity" ]
CNCC(O)c1ccc(O)c(O)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 (salbutamol/albuterol chloride) activates beta-2 adrenergic receptors in cardiac tissue, triggering a mechanistic cascade that increases intracellular cAMP and calcium dysregulation. This leads to generation of afterdepolarizations and cardiac arrhythmias through the established AOP 554 pat...	[ "cardiotoxicity" ]
C[C@H](Cc1c[nH]c2c(OS(C)(=O)=O)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 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" ]
Cn1c(N2CCN(c3ccccn3)CC2)nc2c1c(=O)n(Cc1ccc(Cl)cc1)c(=O)n2C	{ "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 dysregulation in cardiac myocytes. This leads to the generation of early and delayed afterdepolarizations, which promote ectopic electrical activity an...	[ "cardiotoxicity" ]
Cc1ccc(S(=O)(=O)N(C)CC(=O)N2CCN(c3ccccn3)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 dysregulation. This leads to abnormal afterdepolarizations (both early and delayed) that disrupt normal cardiac electrical activity, resulting in arrhyt...	[ "cardiotoxicity" ]
Cn1cnc2ncn(Cc3nc(CCc4ccc(Cl)cc4)no3)c(=O)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 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 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 abnormal afte...	[ "cardiotoxicity" ]
Cl.O=C1COc2c(cc(O)cc2C(O)CNCCc2ccccc2)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 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, triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation in cardiac myocytes. This leads to delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustained arrhythmic activity compromises...	[ "cardiotoxicity" ]
COc1ccc(CC(C)NCC(O)c2ccc(O)c(NC=O)c2)cc1.O.O=C(O)/C=C/C(=O)O	{ "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, triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation in cardiac myocytes. This leads to abnormal cardiac electrical activity characterized by afterdepolarizations and arrhythmias, resulting in cardiotoxic...	[ "cardiotoxicity" ]
COc1ccc(C[C@@H](C)NC[C@H](O)c2ccc(O)c(NC=O)c2)cc1.O.O=C(O)/C=C/C(=O)O	{ "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 mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to generation of delayed and early afterdepolarizations, which precipitate cardiac arrhythmias. Sustained arrhythmias c...	[ "cardiotoxicity" ]
COc1c(CNC[C@H](O)c2ccc(O)c3[nH]c(=O)ccc23)ccc(NC(=O)CCN2CCC(OC(=O)Nc3ccccc3-c3ccccc3)CC2)c1C	{ "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 early and delayed) that disrupt cardiac electrical activity, causing arrhythmias. Susta...	[ "cardiotoxicity" ]
Cc1cc(C)n(-c2nc(SCC(=O)Nc3nccs3)c3c4c(sc3n2)COC(C)(C)C4)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 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 events that increase cAMP levels and calcium dysregulation in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote ectopic electrical activity and car...	[ "cardiotoxicity" ]
Cc1ccccc1CCCNCC(O)c1ccc(O)c2c1OCC(=O)N2.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 the beta-2 adrenergic receptor (ADRB2), triggering a cascade of intracellular signaling that increases cAMP levels and calcium dysregulation in cardiac myocytes. This leads to abnormal afterdepolarizations (both delayed and early), which promote cardiac arrhythmias. Sustained arrh...	[ "cardiotoxicity" ]
COc1cc(NC(=O)CCN2CCC(OC(=O)Nc3ccccc3-c3ccccc3)CC2)ccc1CNC[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 afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through compromised cardiac f...	[ "cardiotoxicity" ]
CS(=O)(=O)Nc1cc([C@@H](O)CNCC2CCN(S(=O)(=O)c3ccc(-n4cc(C(=O)O)cn4)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 elevated intracellular cAMP levels in cardiac myocytes.", "Step 2: Elevate...	{ "Summary": "The compound activates the beta-2 adrenergic receptor (ADRB2), initiating a signaling cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to increased early and delayed afterdepolarizations, which promote cardiac arrhythmias through ectopic activity and re...	[ "cardiotoxicity" ]
COc1ccc(CCCNCC(O)c2cc(O)cc3c2OCC(=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 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 signaling in cardiac myocytes. This dysregulation promotes afterdepolarizations and cardiac arrhythmias through abnormal electrophysiological activity. Sustained arrhythmias...	[ "cardiotoxicity" ]
O=C(CCOCCc1cccc(Cl)c1)N(CCNCCc1ccc(O)c2[nH]c(=O)sc12)CCN1CCCCC1	{ "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 cascade of intracellular signaling events that increase cAMP levels and calcium dysregulation. This leads to the generation of delayed and early afterdepolarizations, which disrupt normal cardiac electrophysiology...	[ "cardiotoxicity" ]
CC(C)CCc1ccc(C(O)CNc2ccc(CCNCC(O)c3ccc(O)c(CO)c3)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 through ectopic...	[ "cardiotoxicity" ]
CC(C)Nc1cc(-c2ccc(CCNC[C@H](O)c3ccccc3)cc2)ccc1C(=O)O	{ "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 (ADRB2), initiating a mechanistic cascade that increases intracellular cAMP levels in cardiac tissue. This elevation in cAMP enhances calcium handling abnormalities through PKA-mediated phosphorylation of calcium regulatory proteins, promoting both d...	[ "cardiotoxicity" ]
C[C@H](Cc1ccc2[nH]c(C(=O)NCC3CCC3)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 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 afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through compromised cardiac e...	[ "cardiotoxicity" ]
CCCOc1cc(-c2ccc(CCN[C@@H](C)[C@H](O)c3ccccc3)cc2)ccc1C(=O)O	{ "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 afterdepolarizations (both early and delayed), which promote ectopic electrical activity and arrhythmias. Sust...	[ "cardiotoxicity" ]
CC(C)N(CC[C@H](c1ccccc1)c1cc(CCCCOc2ccc(CCNC[C@H](O)c3ccc(O)c(CO)c3)cc2)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 (ADRB2), 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 cardiac arrhythmias through ectopic ...	[ "cardiotoxicity" ]
COc1ccc(Nc2ccc(CCNC[C@H](O)c3ccc(O)c4[nH]c(=O)ccc34)cc2)cc1-c1cccc(CN)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 and calcium dysregulation. This leads to abnormal afterdepolarizations and cardiac arrhythmias, ultimately resulting in cardiotoxicity through compromised cardiac f...	[ "cardiotoxicity" ]
CC(C)(C)c1cc(C(c2cccnc2)N2CCN(CCO)CC2)cc(C(C)(C)C)c1O	{ "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 afterdepolarizations (both early and delayed), which promote ectopic electrical activity and arrhythmias. Sust...	[ "cardiotoxicity" ]
CC(=O)O.NS(=O)(=O)c1cccc(COCCOCCCCCCNC[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 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 handling promotes afterdepolarizations (both early and delayed), which generate ectopic electrical activity and ...	[ "cardiotoxicity" ]
Cc1cn([C@H](C)CC#N)c(=O)c2cc(Cn3nc(C(F)F)cc3Cl)nn12	{ "ADRB2": "Activation", "GR": "Activation", "AChE": "Inhibition", "COX1": "Inhibition", "KCNH2": "Inhibition", "SCN5A": "Inhibition" }	[ "Aop:554", "Aop:318", "Aop:559", "Aop:177", "Aop:555", "Aop:553" ]	[ "\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:318\nTitle: Glucocorticoid Receptor activation lead...	[ { "MIE": "ADRB2 Activation", "Reasoning_Steps": [ "Step 1: ADRB2 activation increases intracellular cAMP levels in cardiac myocytes, enhancing calcium handling and electrical excitability.", "Step 2: Elevated cAMP promotes delayed and early afterdepolarizations by increasing spontaneous calcium ...	{ "Summary": "The query compound exhibits multiple mechanisms of cardiotoxicity through dual activation of ADRB2 and GR, combined with inhibition of critical cardiac ion channels (KCNH2, SCN5A) and AChE. ADRB2 activation and AChE inhibition both promote arrhythmias via altered cardiac electrophysiology. KCNH2 and SCN...	[ "kidney toxicity", "cardiotoxicity", "liver toxicity" ]
COc1ccc(CCCNCC(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, 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 electrical ...	[ "cardiotoxicity" ]
CCOCCCNC(=O)c1cc(-c2cccnc2)nc2ccc(S(=O)(=O)N3CCC(C)CC3)cc12	{ "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 dysregulation. This leads to abnormal cardiac electrophysiology characterized by afterdepolarizations and arrhythmias, ultimately resulting in cardiotox...	[ "cardiotoxicity" ]
CS(=O)(=O)Nc1cc([C@@H](O)CNC2CCN(c3ccc(NC(=O)CC(=O)O)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 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 delayed and early afterdepolarizations, which promote cardiac arrhythmias. Sustained arrhythmias compromise cardiac ...	[ "cardiotoxicity" ]
C[C@H](CNc1cccc(-c2ccc(C(=O)O)cc2)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, triggering a cascade of intracellular signaling events that increase cAMP levels and calcium handling dysregulation in cardiac myocytes. This leads to the generation of delayed and early afterdepolarizations, which promote cardiac arrhythmias throug...	[ "cardiotoxicity" ]
CC(C)(Cc1ccc(Oc2ccc(C(N)=O)cn2)cc1)NC[C@H](O)COc1cccc2c1C(Cc1ccccc1)(Cc1ccccc1)C(=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 the beta-2 adrenergic receptor, 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 cardiac arrhythmias through ectopic activ...	[ "cardiotoxicity" ]
Cc1cc(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 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 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, resulting in abnormal ca...	[ "cardiotoxicity" ]
COCCNCc1cccc(CCNC[C@H](O)c2ccc(O)c3[nH]c(=O)sc23)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 abnormal afterdepolarizations (both delayed and early), which promote cardiac arrhythmias. Sustaine...	[ "cardiotoxicity" ]
Cc1cccc(CC(C)(C)NCC(O)c2cc(O)cc3c2OCC(=O)N3)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 mechanistic cascade that increases intracellular cAMP and calcium dysregulation in cardiac myocytes. This leads to afterdepolarizations and cardiac arrhythmias through enhanced automaticity and triggered activity. The resulting electrical ...	[ "cardiotoxicity" ]
CCCn1c(=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 abnormal afterdepolarizations and cardiac arrhythmias through enhanced automaticity and triggered activity. The resulting el...	[ "cardiotoxicity" ]
C[C@H](CNc1cccc(-c2sccc2C(=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 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. Sustained arrhythmic activity compr...	[ "cardiotoxicity" ]
CS(=O)(=O)Nc1cc(OC[C@@H](O)CNCC2CCN(S(=O)(=O)c3ccc(NC(=O)NCc4cc(F)ccc4F)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 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" ]
O=C(CN1C(=O)CCC1=O)Nc1nc(-c2nc3ccccc3s2)cs1	{ "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 early and delayed afterdepolarizations, which promote ectopic electrical...	[ "cardiotoxicity" ]
Cc1ncc(CN2CCCC(C(=O)Nc3ccc(-c4cccc(F)c4)cc3)C2)s1	{ "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 increased afterdepolarizations (both delayed and early), which promote cardiac arrhythmias through ectopic activity and re-e...	[ "cardiotoxicity" ]
CC(=O)O.O=S(=O)(NC1CCCCC1)c1cccc(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 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 dysregulation in cardiac myocytes. This leads to increased afterdepolarizations (both early and delayed), which promote ectopic electrical activity and car...	[ "cardiotoxicity" ]
CC(C)N(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 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, ultimately resulting in cardiotoxic effects characterized by ir...	[ "cardiotoxicity" ]
CC(C)(Cc1ccc(NC(=O)CCCNC(=O)CCN)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 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" ]
O=CNc1cc([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 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 generation of delayed and early afterdepolarizations, which promote ectopic activity and arrhythmogenic re-entry, ul...	[ "cardiotoxicity" ]
C[C@H](Cc1cccc(CC(=O)NCc2ccccc2)c1)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 and calcium dysregulation. This leads to generation of afterdepolarizations and cardiac arrhythmias through altered electrophysiology, resulting in cardiotoxic effe...	[ "cardiotoxicity" ]

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ToxReason

🚀 Accepted at ACL 2026 Findings

ToxReason is a benchmark dataset for mechanistic chemical toxicity reasoning based on Adverse Outcome Pathways (AOPs).

The dataset is designed to evaluate whether large language models can generate biologically interpretable toxicity reasoning trajectories that connect molecular structures, Molecular Initiating Events (MIEs), pathway perturbations, and organ-level adverse outcomes.

Dataset Overview

ToxReason consists of three splits:

Split	Description
`MIE_matched`	Large-scale silver training data constructed by matching chemicals with experimentally supported MIE bioactivity data from ChEMBL.
`MIE_AO_matched`	Higher-quality training data linking MIEs and curated adverse outcomes through biologically related AOP trajectories.
`evaluation`	Evaluation data for assessing mechanistic toxicity reasoning performance.

The benchmark focuses on three major organ toxicity categories:

Liver Toxicity
Cardiotoxicity
Kidney Toxicity

Task Description

Given a molecular structure represented as a SMILES string, models are expected to generate mechanistic toxicity reasoning trajectories.

The expected reasoning may include:

Molecular Initiating Events (MIEs)
Biological pathway perturbations
Adverse Outcome Pathway information
Organ-level adverse outcomes
Stepwise mechanistic toxicity explanations

Intended Use

ToxReason is intended for:

Toxicity reasoning evaluation
Mechanistic toxicity generation
LLM reasoning benchmark research
AI-assisted drug safety assessment
Explainable AI for toxicology

Limitations

The dataset includes reasoning trajectories derived from curated biological knowledge and rule-based construction.
Biological mechanisms may not fully represent all real-world causal toxicity pathways.
The current benchmark focuses on liver, heart, and kidney toxicities.
This dataset should be used for research purposes and should not be considered a substitute for expert toxicological evaluation.

License

This dataset is released under the CC BY 4.0 license.

Citation

If you use this dataset, please cite:

@article{park2026toxreason,
  title={ToxReason: A Benchmark for Mechanistic Chemical Toxicity Reasoning via Adverse Outcome Pathway},
  author={Park, Jueon and Jang, Wonjune and Kim, Chanhwi and Park, Yein and Kang, Jaewoo},
  journal={arXiv preprint arXiv:2604.06264},
  year={2026}
}

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Paper for dmis-lab/ToxReason

ToxReason: A Benchmark for Mechanistic Chemical Toxicity Reasoning via Adverse Outcome Pathway

Paper • 2604.06264 • Published Apr 7 • 4