Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMA16BR)

• Drug Name: Vorapaxar Drug Info
• Synonyms: Vorapaxar; 618385-01-6; Zontivity; SCH-530348; SCH530348; UNII-ZCE93644N2; CHEMBL493982; CHEBI:82702; ZCE93644N2; MK-5348; ethyl ((1R,3aR,4aR,6R,8aR,9S,9aS)-9-((E)-2-(5-(3-fluorophenyl)pyridin-2-yl)vinyl)-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl)carbamate; Ethyl [(1r,3ar,4ar,6r,8ar,9s,9as)-9-{(E)-2-[5-(3-Fluorophenyl)pyridin-2-Yl]ethenyl}-1-Methyl-3-Oxododecahydronaphtho[2,3-C]furan-6-Yl]carbamate; Vorapaxar [USAN:INN]; Carbamic acid, [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(1E)-2-[5-(3-fluorophenyl)-2- pyridinyl]etheny

Indication

Disease Entry	ICD 11	Status	REF
Myocardial infarction	BA41-BA43	Approved	[1]
Stroke	8B20	Investigative	[2]

• Cross-matching ID:
  PubChem CID: 10077130
  ChEBI ID: CHEBI:82702
  CAS Number: CAS 618385-01-6
  TTD Drug ID: DMA16BR
  INTEDE Drug ID: DR1708
  ACDINA Drug ID: D00732

Molecule-Related Drug Atlas

Drug(s) Targeting Proteinase activated receptor 1 (F2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
E5555	DMQERC6	Acute coronary syndrome	BA41	Phase 2	[5]
PZ-128	DMU5H3A	Peripheral arterial occlusive disorder	BD4Z	Phase 2	[6]
RWJ-58259	DMYXD6A	Artery stenosis	BD52	Terminated	[7]
FR-171113	DMIQB9E	Thrombosis	DB61-GB90	Terminated	[8]
SCH-602539	DMRDM9S	Arteriosclerosis	BD40	Investigative	[9]
RWJ-56110	DME07AN	Discovery agent	N.A.	Investigative	[10]
SCH-205831	DM584T6	Thrombosis	DB61-GB90	Investigative	[11]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[12]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[13]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[14]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[15]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[16]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[18]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[19]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[13]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[20]

Drug(s) Metabolized By Cytochrome P450 2J2 (CYP2J2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Riociguat	DMXBLMP	Chronic thromboembolic pulmonary hypertension		Approved	[21]
Rivaroxaban	DMQMBZ1	Deep vein thrombosis	BD71	Approved	[22]
Ergocalciferol	DMHO0AR	Hypoparathyroidism	5A50	Approved	[23]
Vitamin D	DMWQUC9	N. A.	N. A.	Approved	[23]
Alfacalcidol	DM1237M	Hyperparathyroidism	5A51	Phase 4	[23]
Ebastine	DMH21D9	N. A.	N. A.	Phase 4	[24]
MANIDIPINE	DMJPGUA	N. A.	N. A.	Phase 3	[25]
Carebastine	DMUVMWZ	Ocular allergy	4A81	Phase 3	[26]
Eperisone	DM1SMAI	Muscle spasm	MB47.3	Phase 3	[27]
H3B-6545	DMIFCY2	Breast cancer	2C60-2C65	Phase 1/2	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proteinase activated receptor 1 (F2R)	TTL935N	PAR1_HUMAN	Antagonist	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 2J2 (CYP2J2) Main DME	DERSX5P	CP2J2_HUMAN	Substrate	[4]

References

• [1] 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: 4047).
• [2] Vorapaxar FDA Label
• [3] In Process Citation. Pharm Unserer Zeit. 2009;38(4):320-8.
• [4] Vorapaxar: the missing link in antiplatelet therapy! J Anaesthesiol Clin Pharmacol. 2017 Apr-Jun;33(2):269-270.
• [5] Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of Thrombin-Acute Coronary Syndromes Trial. Circulation. 2011 May 3;123(17):1843-53.
• [6] PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study. Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):2990-3003.
• [7] RWJ-58259: a selective antagonist of protease activated receptor-1. Cardiovasc Drug Rev. 2003 Winter;21(4):313-26.
• [8] In vitro antiplatelet profile of FR171113, a novel non-peptide thrombin receptor antagonist. Eur J Pharmacol. 1999 Nov 19;384(2-3):197-202.
• [9] 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. (Target id: 347).
• [10] Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12257-62.
• [11] Himbacine derived thrombin receptor (PAR-1) antagonists: SAR of the pyridine ring. Bioorg Med Chem Lett. 2007 Aug 15;17(16):4509-13.
• [12] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [13] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [14] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [15] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [16] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [17] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [18] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [19] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [20] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [21] Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58.
• [22] Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost. 2010 Mar;103(3):572-85.
• [23] Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroids. 2006 Oct;71(10):849-56.
• [24] Identifying a selective substrate and inhibitor pair for the evaluation of CYP2J2 activity. Drug Metab Dispos. 2012 May;40(5):943-51.
• [25] Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019 Jun 1;306:1-9.
• [26] Characterization of ebastine, hydroxyebastine, and carebastine metabolism by human liver microsomes and expressed cytochrome P450 enzymes: major roles for CYP2J2 and CYP3A. Drug Metab Dispos. 2006 Nov;34(11):1793-7.
• [27] Characterization of human cytochrome P450 enzymes involved in the biotransformation of eperisone. Xenobiotica. 2009 Jan;39(1):1-10.
• [28] Nonclinical pharmacokinetics and in vitro metabolism of H3B-6545, a novel selective ERalpha covalent antagonist (SERCA). Cancer Chemother Pharmacol. 2019 Jan;83(1):151-160.