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

General Information of Drug (ID: DM48QTG)

• Drug Name: Trp-Ile-Ile-Asp-Leu-Hisc(Cys-Ser-Val-Tyr-Phe-Cys) Drug Info
• Synonyms: CHEMBL408141

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 44368903
  TTD Drug ID: DM48QTG

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

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	[2]
Macitentan	DMP79A1	Cardiovascular disease	BA00-BE2Z	Approved	[4]
BQ788	DM6KRLW	Acute kidney injury	GB60	Phase 3	[12]
PD-145065	DMWVBTQ	Hypertension	BA00-BA04	Phase 2	[13]
SPI-1620	DMNPRMC	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]
ENB003	DMK2B3S	Melanoma	2C30	Phase 1/2	[15]
J-104132	DM5E6MK	Pulmonary arterial hypertension	BB01.0	Discontinued in Phase 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]

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	Inhibitor	[1]
Endothelin B receptor (EDNRB)	TT3ZTGU	EDNRB_HUMAN	Inhibitor	[1]

References

• [1] Structure-activity relationships in a series of monocyclic endothelin analogues, Bioorg. Med. Chem. Lett. 4(4):567-572 (1994).
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [4] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [5] Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
• [6] Influence of endothelin receptor antagonists on myocardial protein kinase C isoforms in uraemic cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:276S-279S.
• [7] 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.
• [8] 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.
• [9] Pfizer. Product Development Pipeline. March 31 2009.
• [10] Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats. J Cardiovasc Pharmacol. 2006 Mar;47(3):456-62.
• [11] Endothelin in heart failure: a promising therapeutic target Heart. 1997 Feb;77(2):93-4.
• [12] BQ788, an endothelin ET(B) receptor antagonist, attenuates stab wound injury-induced reactive astrocytes in rat brain. Glia. 1999 May;26(3):268-71.
• [13] 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.
• [14] Clinical pipeline report, company report or official report of Spectrum Phamaceuticals (2009).
• [15] 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.
• [16] 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.
• [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).