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

General Information of Drug (ID: DM5E6MK)

• Drug Name: J-104132 Drug Info
• Synonyms: L-753037; (5S,6R,7R)-2-Butyl-7-[2-[2(S)-carboxypropyl]-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary arterial hypertension	BB01.0	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 186002
  CAS Number: CAS 198279-45-7
  TTD Drug ID: DM5E6MK

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	[3]
Ambrisentan	DMD1QXW	Pulmonary arterial hypertension	BB01.0	Approved	[4]
Macitentan	DMP79A1	Cardiovascular disease	BA00-BE2Z	Approved	[5]
Sparsentan	DMMP51W	IgA nephropathy	MF8Y	Approved	[6]
LU302146	DMMJVXZ	Pulmonary hypertension	BB01	Approved	[7]
Atrasentan	DMM74PK	Diabetic nephropathy	GB61.Z	Phase 3	[8]
Clazosentan	DMQSBX4	Cerebral vasospasm	BA85.Z	Phase 3	[9]
PF-1228305	DMS1EQ7	Pulmonary hypertension	BB01	Phase 3	[10]
Darusentan	DMN8DQH	Hypotension	BA20-BA21	Phase 3	[11]
BQ-123	DM0MO8I	Pulmonary arterial hypertension	BB01.0	Phase 2	[12]

Drug(s) Targeting Endothelin B receptor (EDNRB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[3]
Macitentan	DMP79A1	Cardiovascular disease	BA00-BE2Z	Approved	[5]
BQ788	DM6KRLW	Acute kidney injury	GB60	Phase 3	[13]
PD-145065	DMWVBTQ	Hypertension	BA00-BA04	Phase 2	[14]
SPI-1620	DMNPRMC	Solid tumour/cancer	2A00-2F9Z	Phase 2	[15]
ENB003	DMK2B3S	Melanoma	2C30	Phase 1/2	[16]
ENRASENTAN	DM05F1Z	Pulmonary arterial hypertension	BB01.0	Discontinued in Phase 2	[17]
SB-209670	DMJYW80	Arrhythmia	BC9Z	Discontinued in Phase 2	[18]
ET-1	DMA85ND	N. A.	N. A.	Phase 0	[19]
PD142893	DMFA27N	N. A.	N. A.	Terminated	[20]

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	Modulator	[2]
Endothelin B receptor (EDNRB)	TT3ZTGU	EDNRB_HUMAN	Modulator	[2]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010566)
• [2] Pharmacological properties of J-104132 (L-753,037), a potent, orally active, mixed ETA/ETB endothelin receptor antagonist. J Pharmacol Exp Ther. 1999 Jun;289(3):1262-70.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [5] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [6] Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
• [7] Influence of endothelin receptor antagonists on myocardial protein kinase C isoforms in uraemic cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:276S-279S.
• [8] 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.
• [9] 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.
• [10] Pfizer. Product Development Pipeline. March 31 2009.
• [11] Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats. J Cardiovasc Pharmacol. 2006 Mar;47(3):456-62.
• [12] Endothelin in heart failure: a promising therapeutic target Heart. 1997 Feb;77(2):93-4.
• [13] BQ788, an endothelin ET(B) receptor antagonist, attenuates stab wound injury-induced reactive astrocytes in rat brain. Glia. 1999 May;26(3):268-71.
• [14] Reversal of established responses to endothelin-1 in vivo and in vitro by the endothelin receptor antagonists, BQ-123 and PD 145065. Br J Pharmacol. 1994 May;112(1):207-13.
• [15] Clinical pipeline report, company report or official report of Spectrum Phamaceuticals (2009).
• [16] ClinicalTrials.gov (NCT04205227) A Phase 1/2A Trial of ENB 003 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors. U.S.National Institutes of Health.
• [17] Enrasentan, an antagonist of endothelin receptors. Cardiovasc Drug Rev. 2003 Spring;21(1):1-16.
• [18] Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat. Br J Pharmacol. 1996 May;118(1):198-204.
• [19] IRL 2500: A potent ETB selective endothelin antagonist, Bioorg. Med. Chem. Lett. 6(19):2323-2328 (1996).
• [20] Human optic nerve head astrocytes as a target for endothelin-1. Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2704-13.