Details of the Drug

General Information of Drug (ID: DMKM5HB)

Drug Name

Sitaxsentan

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Pulmonary arterial hypertension	BB01.0	Withdrawn from market	[1], [2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

454.9

Topological Polar Surface Area (xlogp)

3.7

Rotatable Bond Count (rotbonds)

6

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

9

ADMET Property

Absorption: The absorption of drug is 70-100% [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 10 hours [4]
Metabolism: The drug is metabolized via the hepatic [3]

Chemical Identifiers

Formula: C18H15ClN2O6S2
IUPAC Name: N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-[2-(6-methyl-1,3-benzodioxol-5-yl)acetyl]thiophene-3-sulfonamide
Canonical SMILES: CC1=CC2=C(C=C1CC(=O)C3=C(C=CS3)S(=O)(=O)NC4=C(C(=NO4)C)Cl)OCO2
InChI: InChI=1S/C18H15ClN2O6S2/c1-9-5-13-14(26-8-25-13)7-11(9)6-12(22)17-15(3-4-28-17)29(23,24)21-18-16(19)10(2)20-27-18/h3-5,7,21H,6,8H2,1-2H3
InChIKey: PHWXUGHIIBDVKD-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 216235
ChEBI ID: CHEBI:135736
CAS Number: 184036-34-8
DrugBank ID: DB06268
TTD ID: D0T1RG
VARIDT ID: DR00826
INTEDE ID: DR1491

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]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9)_{Main DME}	DE5IED8	CP2C9_HUMAN	Substrate	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Pulmonary arterial hypertension

ICD Disease Classification

BB01.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Endothelin A receptor (EDNRA)	DTT	EDNRA	3.19E-05	-2.69	-1.71
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	4.97E-04	-1.04E+00	-1.67E+00

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

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2	Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
3	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension. Eur J Clin Invest. 2009 Jun;39 Suppl 2:14-8.
6	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.
7	Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
8	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.
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12	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.
13	A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
14	A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
15	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
16	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
17	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
18	Influence of endothelin receptor antagonists on myocardial protein kinase C isoforms in uraemic cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:276S-279S.
19	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.
20	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.
21	Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
22	Pfizer. Product Development Pipeline. March 31 2009.
23	Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats. J Cardiovasc Pharmacol. 2006 Mar;47(3):456-62.
24	Endothelin in heart failure: a promising therapeutic target Heart. 1997 Feb;77(2):93-4.