Details of the Drug

General Information of Drug (ID: DMMP51W)

Drug Name

sparsentan

Synonyms

Sparsentan; RE-021; 254740-64-2; UNII-9242RO5URM; PS433540; PS-433540; CHEMBL539423; 9242RO5URM; BMS-346567; retrophin; Sparsentan [USAN]; compound 7 [PMID 15634011]; PS 33540; Sparsentan (RE-021); Sparsentan(PS433540); SCHEMBL535109; GTPL8448; BCP23969; BDBM50175523; SB16876; DB12548; CS-7947; DARA-a (Dual Acting Receptor Antagonist of angiotension and endothelin receptors); HY-17621; L023324; 4'-((2-butyl-4-oxo-1,3-diazaspiro[44]non-1-en-3-yl)methyl)-N-(4,5-dimethylisoxazol-3-yl)-2'-(ethoxymethyl)-[1,1'-biphenyl]-2-sulfonamide; RE-021

Indication

Disease Entry	ICD 11	Status	REF
Focal segmental glomerulosclerosis	MF8Y	Phase 3	[1]
Hypertension	BA00-BA04	Phase 2	[2]
Myocardial infarction	BA41-BA43	Phase 2	[3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

592.8

Topological Polar Surface Area (xlogp)

5

Rotatable Bond Count (rotbonds)

12

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

8

Chemical Identifiers

Formula: C32H40N4O5S
IUPAC Name: 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-(ethoxymethyl)phenyl]-N-(4,5-dimethyl-1,2-oxazol-3-yl)benzenesulfonamide
Canonical SMILES: CCCCC1=NC2(CCCC2)C(=O)N1CC3=CC(=C(C=C3)C4=CC=CC=C4S(=O)(=O)NC5=NOC(=C5C)C)COCC
InChI: InChI=1S/C32H40N4O5S/c1-5-7-14-29-33-32(17-10-11-18-32)31(37)36(29)20-24-15-16-26(25(19-24)21-40-6-2)27-12-8-9-13-28(27)42(38,39)35-30-22(3)23(4)41-34-30/h8-9,12-13,15-16,19H,5-7,10-11,14,17-18,20-21H2,1-4H3,(H,34,35)
InChIKey: WRFHGDPIDHPWIQ-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 10257882
CAS Number: 254740-64-2
DrugBank ID: DB12548
TTD ID: D0YS1U

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Angiotensin II receptor type-1 (AGTR1)	TT8DBY3	AGTR1_HUMAN	Antagonist	[4]
Endothelin A receptor (EDNRA)	TTKRD0G	EDNRA_HUMAN	Antagonist	[4], [5]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Focal segmental glomerulosclerosis

ICD Disease Classification

MF8Y

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Angiotensin II receptor type-1 (AGTR1)	DTT	AGTR1	8.95E-01	1.34E-02	0.07

Molecular Expression Atlas (MEA)

MEA Detail

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References

1	ClinicalTrials.gov (NCT03493685) Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS) (DUPLEX). U.S. National Institutes of Health.
2	ClinicalTrials.gov (NCT00635232) A Study To Evaluate The Dose-Related Efficacy and Safety of PS433540 in Subjects With Hypertension. U.S. National Institutes of Health.
3	Dual angiotensin II and endothelin A receptor antagonists: synthesis of 2'-substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics. J Med Chem. 2005 Jan 13;48(1):171-9.
4	Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
5	DOI: 10.1038/hr.2009.135
6	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
8	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
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	Reduction of bFGF-induced smooth muscle cell proliferation and endothelin receptor mRNA expression by mevastatin and atorvastatin. Biochem Pharmacol. 2002 Aug 1;64(3):497-505.
16	Radioligand binding assays: application of [(125)I]angiotensin II receptor binding. Methods Mol Biol. 2009;552:131-41.
17	Mechanism of diastolic stiffening of the failing myocardium and its prevention by angiotensin receptor and calcium channel blockers. J Cardiovasc Pharmacol. 2009 Jul;54(1):47-56.
18	Candesartan: widening indications for this angiotensin II receptor blocker Expert Opin Pharmacother. 2009 Aug;10(12):1995-2007.
19	Deletion of angiotensin II type I receptor reduces hepatic steatosis. J Hepatol. 2009 Jun;50(6):1226-35.
20	The amino-terminus of angiotensin II contacts several ectodomains of the angiotensin II receptor AT1. J Med Chem. 2010 Mar 11;53(5):2063-75.
21	Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69.
22	Tasosartan, enoltasosartan, and angiotensin II receptor blockade: the confounding role of protein binding. J Pharmacol Exp Ther. 2000 Nov;295(2):649-54.
23	Clinical profile of eprosartan: a different angiotensin II receptor blocker. Cardiovasc Hematol Agents Med Chem. 2008 Oct;6(4):253-7.