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

General Information of Drug (ID: DMTIQF3)

• Drug Name: Treprostinil Drug Info
• Synonyms: Treprostinilo; Treprostinilum; Uniprost; Viveta; Treprostinil sodium; LRX 15; U 62840; Remodulin (TN); Treprostinil [USAN:INN]; UT-15; Treprostinil (USAN/INN); U-62,840; ((1R,2R,3aS,9aS)-2-hydroxy-1-((3S)-3-hydroxyoctyl)-2,3,3a,4,9,9a-hexahydro-1H-cylopent(b)naphthalen-5-yl)oxy)acetate; ({(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-yl}oxy)acetic acid; 15 AU81; 2-[[(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[g]naphthalen-5-yl]oxy]acetic acid; 2-[[(1S,2S,3aR,9aR)-2-hydroxy-1-[(3R)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[g]naphthalen-5-yl]oxy]acetic acid

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary arterial hypertension	BB01.0	Approved	[1] , [2]

• Therapeutic Class: Antihypertensive Agents
• Cross-matching ID:
  PubChem CID: 6918140
  ChEBI ID: CHEBI:50861
  CAS Number: CAS 81846-19-7
  TTD Drug ID: DMTIQF3
  INTEDE Drug ID: DR1632

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[7]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[7]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[8]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[9]
Diclofenac	DMPIHLS	Osteoarthritis	FA00-FA05	Approved	[10]
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[11]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[7]
Mycophenolate mofetil	DMPQAGE	Organ transplant rejection	NE84	Approved	[12]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[13]

Drug(s) Metabolized By Cytochrome P450 2C9 (CYP2C9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Premature labour	JB00	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[16]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[8]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[8]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[18]
Diclofenac	DMPIHLS	Osteoarthritis	FA00-FA05	Approved	[19]
Estrone	DM5T6US	Menopausal and postmenopausal disorder	GA30	Approved	[20]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[21]

Drug(s) Targeting Prostacyclin receptor (PTGIR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selexipag	DMAHSU0	Pulmonary arterial hypertension	BB01.0	Approved	[22]
Epoprostenol	DMUTYR2	Pulmonary hypertension	BB01	Approved	[23]
Dinoprost Tromethamine	DMXQKSL	Abortion	JA00	Approved	[24]
Misoprostol	DMHVJFK	Medical abortion	JA00.1Z	Approved	[24]
LAROPIPRANT	DM5FABJ	Coronary heart disease	BA80.Z	Phase 4	[25]
Beraprost	DMWL182	Pulmonary hypertension	BB01	Phase 4	[26]
esuberaprost	DMXLGED	Gout	FA25	Phase 3	[27]
Ralinepag	DM7G4Y9	Pulmonary arterial hypertension	BB01.0	Phase 2	[28]
Clinprost	DM6E5VA	Asthma	CA23	Discontinued in Preregistration	[29]
Ataprost	DMPTG39	Asthma	CA23	Discontinued in Phase 3	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostacyclin receptor (PTGIR)	TTOFYT1	PI2R_HUMAN	Agonist	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[4]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[5]

References

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• [2] Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
• [3] Dosing considerations in the use of intravenous prostanoids in pulmonary arterial hypertension: an experience-based review. Am Heart J. 2009 Apr;157(4):625-35.
• [4] Lack of a pharmacokinetic interaction between oral treprostinil and bosentan in healthy adult volunteers. J Clin Pharmacol. 2010 Jul;50(7):829-34.
• [5] FDA label of Treprostinil. The 2020 official website of the U.S. Food and Drug Administration.
• [6] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [7] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
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• [9] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [10] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [11] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [12] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [13] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [14] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [15] Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
• [16] Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
• [17] Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
• [18] Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
• [19] New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
• [20] A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
• [21] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [22] Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012 Oct;40(4):874-80.
• [23] Novel signaling pathways promote a paracrine wave of prostacyclin-induced vascular smooth muscle differentiation. J Mol Cell Cardiol. 2009 May;46(5):682-94.
• [24] Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J Biol Chem. 2003 Feb 28;278(9):6947-58.
• [25] Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydroc... J Med Chem. 2007 Feb 22;50(4):794-806.
• [26] Prostaglandin I2 IP Receptor Agonist, Beraprost, Prevents Transient Global Cerebral Ischemia Induced Hippocampal CA1 Injury in Aging Mice. J Neurol Disord. 2014;2:1000174.
• [27] Specific binding of the new stable epoprostenol analogue beraprost sodium to prostacyclin receptors on human and rat platelets. Arzneimittelforschung. 1989 Apr;39(4):495-9.
• [28] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [29] Protective effect of a prostaglandin I2 analog, TEI-7165, on ischemic neuronal damage in gerbils. Brain Res. 1997 Sep 26;769(2):321-8.
• [30] Pharmacokinetics of intravenous ataprost alfadex, a new prostaglandin I2 analog in healthy volunteers. Int J Clin Pharmacol Ther Toxicol. 1993 Aug;31(8):373-5.