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

General Information of Drug (ID: DMEL5SV)

• Drug Name: FR139317 Drug Info
• Synonyms: D-Alanine, N-((hexahydro-1H-azepin-1-yl)carbonyl)-L-leucyl-1-methyl-D-tryptophyl-3-(2-pyridinyl)-; FR 139317; 142375-60-8; CHEMBL352396; 2-((1-(Hexahydro-1H-azepinyl)carbonyl)amino-4-methylpentanoyl)-3-(-(1-methyl-1H-indolyl)propionyl)amino-3-(2-pyridyl)propionic acid; D-Alanine, N-(N-(N-((hexahydro-1H-azepin-1-yl)carbonyl)-L-leucyl)-1-methyl-D-tryptophyl)-3-(2-pyridinyl)-; GSK424887

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Phase 2	[1]
Anxiety disorder	6B00-6B0Z	Discontinued in Phase 1	[2]
Depression	6A70-6A7Z	Discontinued in Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 107810
  CAS Number: CAS 142375-60-8
  TTD Drug ID: DMEL5SV

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	[5]
Ambrisentan	DMD1QXW	Pulmonary arterial hypertension	BB01.0	Approved	[4]
Macitentan	DMP79A1	Cardiovascular disease	BA00-BE2Z	Approved	[6]
Sparsentan	DMMP51W	IgA nephropathy	MF8Y	Approved	[7]
LU302146	DMMJVXZ	Pulmonary hypertension	BB01	Approved	[8]
Atrasentan	DMM74PK	Diabetic nephropathy	GB61.Z	Phase 3	[9]
Clazosentan	DMQSBX4	Cerebral vasospasm	BA85.Z	Phase 3	[10]
PF-1228305	DMS1EQ7	Pulmonary hypertension	BB01	Phase 3	[11]
Darusentan	DMN8DQH	Hypotension	BA20-BA21	Phase 3	[12]
BQ-123	DM0MO8I	Pulmonary arterial hypertension	BB01.0	Phase 2	[13]

Drug(s) Targeting Substance-P receptor (TACR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[14]
Selegiline	DM6034S	Major depressive disorder	6A70.3	Approved	[4]
Rolapitant	DM8XP26	Chemotherapy-induced nausea	MD90	Approved	[15]
Netupitant	DMEKAYI	Chemotherapy-induced nausea	MD90	Phase 3	[15]
Serlopitant	DM5VH6U	Prurigo nodularis	EC91.0	Phase 3	[16]
LY-686017	DM7WORZ	Atopic dermatitis	EA80	Phase 3	[17]
Elinzanetant	DMC6EFI	Hot flushes	GA30	Phase 3	[18]
CP-122721	DMSWLM5	Major depressive disorder	6A70.3	Phase 2	[19]
VOFOPITANT HYDROCHLORIDE	DMQMYP5	Vomiting	MD90	Phase 2	[20]
LY-2590443	DM81UJW	Migraine	8A80	Phase 2	[21]

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	[3]
Substance-P receptor (TACR1)	TTZPO1L	NK1R_HUMAN	Antagonist	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 998).
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027682)
• [3] 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.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [7] Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
• [8] Influence of endothelin receptor antagonists on myocardial protein kinase C isoforms in uraemic cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:276S-279S.
• [9] 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.
• [10] 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.
• [11] Pfizer. Product Development Pipeline. March 31 2009.
• [12] Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats. J Cardiovasc Pharmacol. 2006 Mar;47(3):456-62.
• [13] Endothelin in heart failure: a promising therapeutic target Heart. 1997 Feb;77(2):93-4.
• [14] Potent, brain-penetrant, hydroisoindoline-based human neurokinin-1 receptor antagonists. J Med Chem. 2009 May 14;52(9):3039-46.
• [15] Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44.
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Stress-related neuropeptides and alcoholism: CRH, NPY and beyond. Alcohol. 2009 November; 43(7): 491-498.
• [18] Elinzanetant (NT-814), a Neurokinin 1,3 Receptor Antagonist, Reduces Estradiol and Progesterone in Healthy Women. J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3221-e3234.
• [19] A review of drug options in age-related macular degeneration therapy and potential new agents. Expert Opin Pharmacother. 2006 Dec;7(17):2355-68.
• [20] Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenicchemotherapy: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jun;10(6):549-58.
• [21] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 360).