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

General Information of Drug (ID: DMMP51W)

• Drug Name: sparsentan Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 10257882
  CAS Number: CAS 254740-64-2
  TTD Drug ID: DMMP51W

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	[6]
Ambrisentan	DMD1QXW	Pulmonary arterial hypertension	BB01.0	Approved	[7]
Macitentan	DMP79A1	Cardiovascular disease	BA00-BE2Z	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]
FR139317	DMEL5SV	Hypertension	BA00-BA04	Phase 2	[15]

Drug(s) Targeting Angiotensin II receptor type-1 (AGTR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Losartan	DM72JXH	Hypertension	BA00-BA04	Approved	[16]
Olmesartan medoxomil	DMWBHRY	High blood pressure	BA00	Approved	[17]
Irbesartan	DMTP1DC	Hypertension	BA00-BA04	Approved	[16]
Valsartan	DMREUQ6	Hypertension	BA00-BA04	Approved	[16]
Candesartan	DMRK8OT	Hypertension	BA00-BA04	Approved	[18]
Telmisartan	DMS3GX2	Hypertension	BA00-BA04	Approved	[19]
Angiotensin Ii	DMLWQ27	Increase blood pressure	BA04	Approved	[20]
SARALASIN	DMKS1DV	Hypertension	BA00-BA04	Approved	[21]
Tasosartan	DMM13DI	Hypertension	BA00-BA04	Approved	[22]
Eprosartan	DM07K2I	Hypertension	BA00-BA04	Approved	[23]

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]

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.