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

General Information of Drug (ID: DM1V329)

• Drug Name: Conivaptan Drug Info
• Synonyms: Conivaptan [INN]; YM 087; YM087; Conivaptan (INN); Vaprisol (TN); YM-087; N-[4-(2-methyl-4,5-dihydro-3H-imidazo[4,5-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamide; N-{4-[(2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl]phenyl}biphenyl-2-carboxamide; 4'-((4,5-dihydro-2-methylimidazo(4,5-d)(1)benzazepin-6(1H)-yl)carbonyl)-2-biphenylcarboxanilide

Indication

Disease Entry	ICD 11	Status	REF
Euvolemic hyponatremia	5C72	Approved	[1]

• Cross-matching ID:
  PubChem CID: 151171
  ChEBI ID: CHEBI:681850
  CAS Number: CAS 210101-16-9
  TTD Drug ID: DM1V329
  INTEDE Drug ID: DR0376

Molecule-Related Drug Atlas

Drug(s) Targeting Vasopressin V2 receptor (V2R)

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]
Tolvaptan	DMIWFRL	Autosomal dominant polycystic kidney disease	GB81	Approved	[7]
Vasopressin	DMQ2FPC	Diabetes insipidus	5A61.5	Approved	[8]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[9]
Lixivaptan	DMDN4ZP	Hyponatraemia	5C72	Phase 3	[10]
Satavaptan	DME5PN3	Acute and chronic heart failure	BD1Z	Phase 3	[11]
SSR149415	DMCMD93	Anxiety disorder	6B00-6B0Z	Phase 2	[12]
ASP-7035	DMTF24A	Nocturia	MF55	Phase 2	[13]

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	[14]
Oxytocin	DMDL27I	Autism spectrum disorder	6A02	Approved	[15]
Felypressin	DMHLP9C	Localisation	N.A.	Approved	[16]
Terlipressin	DMT9FH3	Hypertension	BA00-BA04	Approved	[17]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[9]
Balovaptan	DMKMTDG	Autism spectrum disorder	6A02	Phase 3	[18]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[19]
SSR149415	DMCMD93	Anxiety disorder	6B00-6B0Z	Phase 2	[12]
VA-111913	DMAYWXD	Dysmenorrhea	GA34.3	Phase 2	[20]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[21]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[22]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[23]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[24]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[25]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[27]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[28]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[22]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[29]

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	Modulator	[2]
Vasopressin V2 receptor (V2R)	TTK8R02	V2R_HUMAN	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[3]

References

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• [2] 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.
• [3] Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79.
• [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 receptor antagonists: development of selective and orally active V1a, V2 and V1b receptor ligands. Prog Brain Res. 2002;139:197-210.
• [6] 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).
• [7] Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009 May 1;419(3):577-84.
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• [9] The discovery of GSK221149A: a potent and selective oxytocin antagonist. Bioorg Med Chem Lett. 2008 Jan 1;18(1):90-4.
• [10] Emerging drugs for acute and chronic heart failure: current and future developments. Expert Opin Emerg Drugs. 2007 Mar;12(1):75-95.
• [11] 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.
• [12] Tetrahydroquinoline sulfonamides as vasopressin 1b receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6018-22.
• [13] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030285)
• [14] Nonpeptide vasopressin antagonists: a new group of hormone blockers entering the scene. Exp Clin Endocrinol Diabetes. 1999;107(3):157-65.
• [15] 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.
• [16] 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.
• [17] Investigational vasopressin receptor modulators in the pipeline. Expert Opin Investig Drugs. 2009 Aug;18(8):1119-31.
• [18] 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.
• [19] 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.
• [20] Clinical pipeline report, company report or official report of Avarx.
• [21] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [22] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [23] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [24] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [25] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [26] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [27] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [28] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [29] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.