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

General Information of Drug (ID: DMCMD93)

• Drug Name: SSR149415 Drug Info
• Synonyms: Nelivaptan; SSR 149415; 439687-69-1; UNII-3TY57MQ4OA; SR-149415; SSR-149415; 3TY57MQ4OA; CHEMBL582857; Nelivaptan [INN]; DSSTox_CID_27358; DSSTox_RID_82294; DSSTox_GSID_47358; GTPL2202; DTXSID7047358; SCHEMBL14517029; MolPort-042-665-640; Tox21_300240; BDBM50299343; ZINC42833251; DB12643; SSR-149,415; NCGC00254222-01; NCGC00247960-01; CAS-439687-69-1; (2S,4R)-1-[(3R)-5-chloro-1-(2,4-dimethoxyphenyl)sulfonyl-3-(2-methoxyphenyl)-2-oxoindol-3-yl]-4-hydroxy-N,N-dimethylpyrrolidine-2-carboxamide; Nelivaptan; 1-(5-chloro-1-((2,4-dimethoxyphenyl)sulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide

Indication

Disease Entry	ICD 11	Status	REF
Anxiety disorder	6B00-6B0Z	Phase 2	[1]
Major depressive disorder	6A70.3	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 9895468
  CAS Number: CAS 439687-69-1
  TTD Drug ID: DMCMD93

Molecule-Related Drug Atlas

Drug(s) Targeting Vasopressin V1b receptor (V1BR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Desmopressin	DMS3GVE	Diabetic complication	5A2Y	Approved	[5]
Mozavaptan	DMZ905C	Hyponatraemia	5C72	Approved	[6]
Oxytocin	DMDL27I	Autism spectrum disorder	6A02	Approved	[7]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[8]
ABT-436	DMNAU1V	Anxiety disorder	6B00-6B0Z	Phase 2	[9]
ARGENINE VASOPRESSIN	DM8KN0Q	Discovery agent	N.A.	Investigative	[10]
D[Arg4,Orn8]VP	DM8D4QT	Discovery agent	N.A.	Investigative	[10]
D[Leu4,Lys8]VP	DMDBU7Q	Discovery agent	N.A.	Investigative	[10]
D[Arg4,Lys8]VP	DM69OVM	Discovery agent	N.A.	Investigative	[10]
D[Cha4,Lys8]VP	DM0GO7U	Discovery agent	N.A.	Investigative	[10]

Drug(s) Targeting Vasopressin V2 receptor (V2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Desmopressin	DMS3GVE	Diabetic complication	5A2Y	Approved	[5]
Mozavaptan	DMZ905C	Hyponatraemia	5C72	Approved	[11]
Oxytocin	DMDL27I	Autism spectrum disorder	6A02	Approved	[12]
Tolvaptan	DMIWFRL	Autosomal dominant polycystic kidney disease	GB81	Approved	[13]
Conivaptan	DM1V329	Euvolemic hyponatremia	5C72	Approved	[14]
Vasopressin	DMQ2FPC	Diabetes insipidus	5A61.5	Approved	[15]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[8]
Lixivaptan	DMDN4ZP	Hyponatraemia	5C72	Phase 3	[16]
Satavaptan	DME5PN3	Acute and chronic heart failure	BD1Z	Phase 3	[17]
ASP-7035	DMTF24A	Nocturia	MF55	Phase 2	[18]

Drug(s) Targeting Vasopressin V1a receptor (V1AR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Desmopressin	DMS3GVE	Diabetic complication	5A2Y	Approved	[5]
Mozavaptan	DMZ905C	Hyponatraemia	5C72	Approved	[19]
Oxytocin	DMDL27I	Autism spectrum disorder	6A02	Approved	[20]
Conivaptan	DM1V329	Euvolemic hyponatremia	5C72	Approved	[14]
Felypressin	DMHLP9C	Localisation	N.A.	Approved	[21]
Terlipressin	DMT9FH3	Hypertension	BA00-BA04	Approved	[22]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[8]
Balovaptan	DMKMTDG	Autism spectrum disorder	6A02	Phase 3	[23]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[24]
VA-111913	DMAYWXD	Dysmenorrhea	GA34.3	Phase 2	[25]

Drug(s) Targeting Oxytocin receptor (OTR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Desmopressin	DMS3GVE	Diabetic complication	5A2Y	Approved	[5]
Oxytocin	DMDL27I	Autism spectrum disorder	6A02	Approved	[26]
Carbetocin	DMUSLW3	Postpartum haemorrhage	JA43	Approved	[21]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[27]
Retosiban	DMOYGZF	Preterm labour	JB00	Phase 3	[28]
Barusiban	DMWI0X3	Androgen deficiency	5A81.1	Phase 2	[29]
FE-202767	DMDGZ1C	Erectile dysfunction	HA01.1	Phase 2	[26]
GSK-557296	DM3ZL2O	Premature ejaculation	HA03.0Z	Phase 2	[30]
Pyrrolidine derivative 13	DM3VA8P	N. A.	N. A.	Patented	[31]
PMID28906174-Compound-figure1g	DMECU90	N. A.	N. A.	Patented	[31]

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	[32]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[33]
Rhucin	DM3ADGP	Erectile dysfunction	HA01.1	Approved	[34]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[35]
Miglustat	DM5J64S	Niemann-Pick disease type C		Approved	[36]
Glibenclamide	DM8JXPZ	Diabetic complication	5A2Y	Approved	[37]
Milrinone	DM8TUPF	Congestive heart failure	BD10	Approved	[34]
Oxidized glutathione	DM9EQC0	Breast cancer	2C60-2C65	Approved	[38]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[38]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[39]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Oxytocin receptor (OTR)	TTSCIUP	OXYR_HUMAN	Inhibitor	[2]
Vasopressin V1a receptor (V1AR)	TT4TFGN	V1AR_HUMAN	Inhibitor	[2]
Vasopressin V1b receptor (V1BR)	TTL9MHW	V1BR_HUMAN	Antagonist	[3]
Vasopressin V2 receptor (V2R)	TTK8R02	V2R_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	[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: 2202).
• [2] Tetrahydroquinoline sulfonamides as vasopressin 1b receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6018-22.
• [3] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [4] 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.
• [5] 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.
• [6] New analgesic drugs derived from phencyclidine. J Med Chem. 1981 May;24(5):496-9.
• [7] The human V3 pituitary vasopressin receptor: ligand binding profile and density-dependent signaling pathways. Endocrinology. 1997 Oct;138(10):4109-22.
• [8] The discovery of GSK221149A: a potent and selective oxytocin antagonist. Bioorg Med Chem Lett. 2008 Jan 1;18(1):90-4.
• [9] The vasopressin Avprlb receptor: Molecular and pharmacological studies. Stress. 2011 January; 14(1): 98-115.
• [10] Design and synthesis of the first selective agonists for the rat vasopressin V(1b) receptor: based on modifications of deamino-[Cys1]arginine vasop... J Med Chem. 2007 Feb 22;50(4):835-47.
• [11] Nonpeptide vasopressin receptor antagonists: development of selective and orally active V1a, V2 and V1b receptor ligands. Prog Brain Res. 2002;139:197-210.
• [12] 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: 368).
• [13] Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009 May 1;419(3):577-84.
• [14] 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.
• [15] Vasopressin receptors: structure/function relationships and signal transduction in target cells. J Soc Biol. 2005;199(4):351-9.
• [16] Emerging drugs for acute and chronic heart failure: current and future developments. Expert Opin Emerg Drugs. 2007 Mar;12(1):75-95.
• [17] Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypanosomal chemical entities. Biochem J. 2009 Apr 15;419(2):507-17.
• [18] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030285)
• [19] Nonpeptide vasopressin antagonists: a new group of hormone blockers entering the scene. Exp Clin Endocrinol Diabetes. 1999;107(3):157-65.
• [20] 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.
• [21] 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.
• [22] Investigational vasopressin receptor modulators in the pipeline. Expert Opin Investig Drugs. 2009 Aug;18(8):1119-31.
• [23] 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.
• [24] 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.
• [25] Clinical pipeline report, company report or official report of Avarx.
• [26] 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: 369).
• [27] Pyridobenzodiazepines: a novel class of orally active, vasopressin V2 receptor selective agonists. Bioorg Med Chem Lett. 2006 Feb 15;16(4):954-9.
• [28] The Effect of an Oxytocin Receptor Antagonist (Retosiban, GSK221149A) on the Response of Human Myometrial Explants to Prolonged Mechanical Stretch.Endocrinology.2015 Oct;156(10):3511-6.
• [29] The effect of barusiban, a selective oxytocin antagonist, in threatened preterm labor at late gestational age: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol. 2009 Jun;200(6):627.e1-10.
• [30] Inhibition of ejaculation by the non-peptide oxytocin receptor antagonist GSK557296: a multi-level site of action. Br J Pharmacol. 2013 Aug;169(7):1477-85.
• [31] A patent review of oxytocin receptor antagonists 2013-2017.Expert Opin Ther Pat. 2017 Dec;27(12):1287-1290.
• [32] 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.
• [33] 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.
• [34] 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.
• [35] 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.
• [36] 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.
• [37] 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.
• [38] 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.
• [39] 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.