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

General Information of Drug (ID: DM3AWPB)

• Drug Name: Relcovaptan Drug Info
• Synonyms: SR 49059; SR-49059; Relcovaptan [INN]; 150375-75-0; UNII-C1GL8G6G0O; SR49059; C1GL8G6G0O; CHEMBL419667; 1-(5-Chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzenesulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl)pyrrolidine-2-carboxamide; (2S)-1-[[(2R,3S)-5-CHLORO-3-(2-CHLOROPHENYL)-1-[(3,4-DIMETHOXYPHENYL)SULFONYL]-2,3-DIHYDRO-3-HYDROXY-1H-INDOL-2-YL]CARBONYL]-2-PYRROLIDINECARBOXAMIDE; 2-Pyrrolidinecarboxamide,; [3H]relcovaptan

Indication

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

• Cross-matching ID:
  PubChem CID: 60943
  ChEBI ID: CHEBI:93701
  CAS Number: CAS 150375-75-0
  TTD Drug ID: DM3AWPB

Molecule-Related Drug Atlas

Drug(s) Targeting Vasopressin V1a receptor (V1AR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Desmopressin	DMS3GVE	Diabetic complication	5A2Y	Approved	[4]
Mozavaptan	DMZ905C	Hyponatraemia	5C72	Approved	[5]
Oxytocin	DMDL27I	Autism spectrum disorder	6A02	Approved	[6]
Conivaptan	DM1V329	Euvolemic hyponatremia	5C72	Approved	[7]
Felypressin	DMHLP9C	Localisation	N.A.	Approved	[8]
Terlipressin	DMT9FH3	Hypertension	BA00-BA04	Approved	[9]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[10]
Balovaptan	DMKMTDG	Autism spectrum disorder	6A02	Phase 3	[11]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[12]
SSR149415	DMCMD93	Anxiety disorder	6B00-6B0Z	Phase 2	[13]

Drug(s) Affected By Cystic fibrosis transmembrane conductance regulator (CFTR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ivacaftor	DMZC1HS	Cystic fibrosis	CA25	Approved	[14]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Rhucin	DM3ADGP	Erectile dysfunction	HA01.1	Approved	[16]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[17]
Miglustat	DM5J64S	Niemann-Pick disease type C		Approved	[18]
Glibenclamide	DM8JXPZ	Diabetic complication	5A2Y	Approved	[19]
Milrinone	DM8TUPF	Congestive heart failure	BD10	Approved	[16]
Oxidized glutathione	DM9EQC0	Breast cancer	2C60-2C65	Approved	[20]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[20]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vasopressin V1a receptor (V1AR)	TT4TFGN	V1AR_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Gene/Protein Processing	[3]

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: 3482).
• [2] Binding of [3H] SR 49059, a potent nonpeptide vasopressin V1a antagonist, to rat and human liver membranes. Biochem Biophys Res Commun. 1994 Feb 28;199(1):353-60.
• [3] Vasotocin and vasopressin stimulation of the chloride secretion in the human bronchial epithelial cell line, 16HBE14o-. Br J Pharmacol. 2005 Apr;144(8):1037-50. doi: 10.1038/sj.bjp.0706103.
• [4] Design of potent and selective agonists for the human vasopressin V1b receptor based on modifications of [deamino-cys1]arginine vasopressin at position 4. J Med Chem. 2004 Apr 22;47(9):2375-88.
• [5] Nonpeptide vasopressin antagonists: a new group of hormone blockers entering the scene. Exp Clin Endocrinol Diabetes. 1999;107(3):157-65.
• [6] Mapping peptide-binding domains of the human V1a vasopressin receptor with a photoactivatable linear peptide antagonist. J Biol Chem. 1997 Oct 17;272(42):26536-44.
• [7] Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. Circulation. 2001 Nov 13;104(20):2417-23.
• [8] Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents. Prog Brain Res. 2008;170:473-512.
• [9] Investigational vasopressin receptor modulators in the pipeline. Expert Opin Investig Drugs. 2009 Aug;18(8):1119-31.
• [10] The discovery of GSK221149A: a potent and selective oxytocin antagonist. Bioorg Med Chem Lett. 2008 Jan 1;18(1):90-4.
• [11] Discovery of Balovaptan, a Vasopressin 1a Receptor Antagonist for the Treatment of Autism Spectrum Disorder. J Med Chem. 2020 Feb 27;63(4):1511-1525.
• [12] Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92.
• [13] Tetrahydroquinoline sulfonamides as vasopressin 1b receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6018-22.
• [14] Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010 Nov 18;363(21):1991-2003. doi: 10.1056/NEJMoa0909825.
• [15] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [16] Adenosine receptors and phosphodiesterase inhibitors stimulate Cl- secretion in Calu-3 cells. Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):410-8. doi: 10.1165/rcmb.2002-0247OC. Epub 2003 Apr 24.
• [17] Modulation of deltaF508 cystic fibrosis transmembrane regulator trafficking and function with 4-phenylbutyrate and flavonoids. Am J Respir Cell Mol Biol. 2004 Sep;31(3):351-7. doi: 10.1165/rcmb.2002-0086OC. Epub 2004 Jun 10.
• [18] Proteasome-dependent pharmacological rescue of cystic fibrosis transmembrane conductance regulator revealed by mutation of glycine 622. J Pharmacol Exp Ther. 2008 Apr;325(1):89-99. doi: 10.1124/jpet.107.134502. Epub 2008 Jan 29.
• [19] Comparative pharmacology of the activity of wild-type and G551D mutated CFTR chloride channel: effect of the benzimidazolone derivative NS004. J Membr Biol. 2003 Jul 15;194(2):109-17. doi: 10.1007/s00232-003-2030-z.
• [20] Reversible silencing of CFTR chloride channels by glutathionylation. J Gen Physiol. 2005 Feb;125(2):127-41. doi: 10.1085/jgp.200409115. Epub 2005 Jan 18.
• [21] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.