Details of the Drug Combination

General Information of Drug Combination (ID: DC7RF5D)

• Drug Combination Name: Prasugrel + Brilinta
• Indication: Atrial Fibrillation; Status: Phase 3 [1]
• Component Drugs:
  Prasugrel (DM7MT6E): Small molecular drug
  Brilinta (DMBR01X): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Prasugrel

Disease Entry	ICD 11	Status	REF
Acute coronary syndrome	BA41	Approved	[2]

Prasugrel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
P2Y purinoceptor 12 (P2RY12)	TTZ1DT0	P2Y12_HUMAN	Inhibitor	[7]

Prasugrel Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[8]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[8]

Indication(s) of Brilinta

Disease Entry	ICD 11	Status	REF
Acute coronary syndrome	BA41	Approved	[3]
Thrombosis	DB61-GB90	Approved	[4]
Arterial thrombosis	DB61-DD30	Phase 3	[5]
Myocardial infarction	BA41-BA43	Phase 3	[5]
Peripheral vascular disease	BD4Z	Investigative	[6]

Brilinta Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
P2Y purinoceptor 12 (P2RY12)	TTZ1DT0	P2Y12_HUMAN	Antagonist	[10]

Brilinta Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]

Brilinta Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]

Brilinta Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Terminal nucleotidyltransferase 4A (TENT4A)	OT0G3KR0	PAPD7_HUMAN	Increases ADR	[13]
CD9 antigen (CD9)	OT2184XU	CD9_HUMAN	Increases ADR	[13]
Ephrin type-A receptor 4 (EPHA4)	OT3AMK0C	EPHA4_HUMAN	Increases ADR	[13]
Aryl-hydrocarbon-interacting protein-like 1 (AIPL1)	OT4VBD78	AIPL1_HUMAN	Increases ADR	[14]
Actin-related protein 2/3 complex subunit 1A (ARPC1A)	OTAEEXGQ	ARC1A_HUMAN	Increases ADR	[9]
Putative protein CASTOR3P (GATS)	OTDYE3XK	CAST3_HUMAN	Increases ADR	[9]
LIM domain kinase 2 (LIMK2)	OTRJD7VZ	LIMK2_HUMAN	Increases ADR	[13]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases ADR	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Cardiovascular Diseases	DC3EC39	N. A.	Phase 4	[15]
Myocardial Infarction	DCKXNMR	N. A.	Phase 4	[16]
Coronary Artery Disease	DC963XW	N. A.	Phase 4	[17]
ST-Elevation Myocardial Infarction	DCH6MMX	N. A.	Phase 1	[18]

References

• [1] ClinicalTrials.gov (NCT02866175) Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7562).
• [3] Ticagrelor-Induced Syncope/Bradyarrhythmia. Cureus. 2021 Jan 23;13(1):e12874.
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1765).
• [5] ClinicalTrials.gov (NCT01732822) A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease. U.S. National Institutes of Health.
• [6] Antithrombotic Therapy for Symptomatic Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis. Drugs. 2022 Aug;82(12):1287-1302.
• [7] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [8] The evolution of antiplatelet therapy in the treatment of acute coronary syndromes: from aspirin to the present day. Drugs. 2012 Nov 12;72(16):2087-116.
• [9] Effect of genetic variations on ticagrelor plasma levels and clinical outcomes. Eur Heart J. 2015 Aug 1;36(29):1901-12.
• [10] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [11] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [12] Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. 2010 Sep;38(9):1514-21.
• [13] Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy. J Med Genet. 2013 Sep;50(9):599-605. doi: 10.1136/jmedgenet-2012-101466. Epub 2013 Jun 17.
• [14] Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy. Clin Cancer Res. 2015 Oct 1;21(19):4337-46. doi: 10.1158/1078-0432.CCR-15-0133. Epub 2015 May 26.
• [15] ClinicalTrials.gov (NCT02587260) Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans (HI-TECH)
• [16] ClinicalTrials.gov (NCT02545933) Vorapaxar in Patients With Prior Myocardial Infarction Treated With Prasugrel and Ticagrelor
• [17] ClinicalTrials.gov (NCT01957540) Differential Effect of Ticagrelor Versus Prasugrel Maintenance Dose on Endothelial Function of Peripheral Vessels in Patients With Coronary Artery Disease
• [18] ClinicalTrials.gov (NCT01531114) PraSugrel vs TicagrElor in ST-Elevation Myocardial Infarction paTients With Diabetes Mellitus