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

General Information of Drug (ID: DMKM5HB)

• Drug Name: Sitaxsentan Drug Info
• Synonyms: Sitaxentan; IPI 1040; TBC 11251; TBC11251; Sitaxentan (INN); TBC-11251; N-(4-Chloro-3-methyl-5-isoxazolyl)-2-((2-methyl-4,5-methylenedioxyphenyl)acetyl)thiophene-3-sulfonamide; N-(4-Chloro-3-methyl-5-isoxazolyl)-2-((3,4-(methylenedioxy)-6-methylphenyl)acetyl)-3-thiophenesulfonamide; N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-[2-(6-methyl-1,3-benzodioxol-5-yl)acetyl]thiophene-3-sulfonamide

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary arterial hypertension	BB01.0	Withdrawn from market	[1]

• Cross-matching ID:
  PubChem CID: 216235
  ChEBI ID: CHEMBL282724
  CAS Number: CAS 184036-34-8
  TTD Drug ID: DMKM5HB
  VARIDT Drug ID: DR00826
  INTEDE Drug ID: DR1491

Molecule-Related Drug Atlas

Drug(s) Targeting Endothelin A receptor (EDNRA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[5]
Ambrisentan	DMD1QXW	Pulmonary arterial hypertension	BB01.0	Approved	[6]
Macitentan	DMP79A1	Cardiovascular disease	BA00-BE2Z	Approved	[7]
Sparsentan	DMMP51W	IgA nephropathy	MF8Y	Approved	[8]
LU302146	DMMJVXZ	Pulmonary hypertension	BB01	Approved	[9]
Atrasentan	DMM74PK	Diabetic nephropathy	GB61.Z	Phase 3	[10]
Clazosentan	DMQSBX4	Cerebral vasospasm	BA85.Z	Phase 3	[11]
PF-1228305	DMS1EQ7	Pulmonary hypertension	BB01	Phase 3	[12]
Darusentan	DMN8DQH	Hypotension	BA20-BA21	Phase 3	[13]
BQ-123	DM0MO8I	Pulmonary arterial hypertension	BB01.0	Phase 2	[14]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[18]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[20]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[21]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[23]

Drug(s) Affected By Bile salt export pump (ABCB11)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[24]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[25]
Glipizide	DMZA5PQ	Diabetic complication	5A2Y	Approved	[25]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[26]
Indinavir	DM0T3YH	Human immunodeficiency virus infection	1C62	Approved	[24]
Ofloxacin	DM0VQN3	Acute gonococcal cervicitis		Approved	[25]
Primidone	DM0WX6I	Epilepsy	8A60-8A68	Approved	[27]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[24]
Drospirenone	DM1A9W3	Acne vulgaris	ED80	Approved	[4]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[24]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Endothelin A receptor (EDNRA)	TTKRD0G	EDNRA_HUMAN	Antagonist	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9) Main DME	DE5IED8	CP2C9_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[4]

References

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• [2] Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
• [3] Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension. Eur J Clin Invest. 2009 Jun;39 Suppl 2:14-8.
• [4] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [7] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [8] Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
• [9] Influence of endothelin receptor antagonists on myocardial protein kinase C isoforms in uraemic cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:276S-279S.
• [10] Effects of a selective ET(A)-receptor antagonist, atrasentan (ABT-627), in murine models of allergic asthma: demonstration of mouse strain specificity. Clin Sci (Lond). 2002 Aug;103 Suppl 48:367S-370S.
• [11] Effects of the selective endothelin A (ET(A)) receptor antagonist Clazosentan on cerebral perfusion and cerebral oxygenation following severe subar... Acta Neurochir (Wien). 2007;149(9):911-8; discussion 918.
• [12] Pfizer. Product Development Pipeline. March 31 2009.
• [13] Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats. J Cardiovasc Pharmacol. 2006 Mar;47(3):456-62.
• [14] Endothelin in heart failure: a promising therapeutic target Heart. 1997 Feb;77(2):93-4.
• [15] 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.
• [16] Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
• [17] 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.
• [18] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [19] Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
• [20] Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
• [21] 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.
• [22] A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
• [23] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [24] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [25] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [26] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [27] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.