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

General Information of Drug (ID: DMHW2DU)

• Drug Name: Hoo-Phe-Orn-Pro-hle-Pff-Phe-NH2 Drug Info

Indication

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

• Cross-matching ID:
  PubChem CID: 73347136
  TTD Drug ID: DMHW2DU

Molecule-Related Drug Atlas

Drug(s) Targeting Substance-K receptor (TACR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ibodutant	DMT67EH	Irritable bowel syndrome	DD91.0	Phase 3	[2]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[1]
Rambazole	DMP2DNS	Psoriasis vulgaris	EA90	Phase 2	[3]
Nepadutant	DMPMF6L	Infantile colics	DD93.1	Phase 1/2	[4]
Saredutant	DMSRJY3	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[5]
CS-003	DM1AEVT	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[6]
FK-224	DM1JUS0	Asthma	CA23	Discontinued in Phase 2	[7]
DNK-333	DM4ZO01	Irritable bowel syndrome	DD91.0	Discontinued in Phase 2	[8]
AVE-5883	DM3P84V	Asthma	CA23	Discontinued in Phase 1/2	[9]
UK-224671	DMDTRJB	Urinary incontinence	MF50.2	Discontinued in Phase 1	[10]

Drug(s) Targeting Melanocortin receptor 4 (MC4R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methylnaltrexone bromide	DMZTGN2	Opioid-induced constipation	DB32.1	Approved	[11]
Bremelanotide	DM20LIM	Hypoactive sexual desire dysfunction	HA00	Approved	[12]
Setmelanotide	DMPVRN9	Obesity	5B81	Approved	[13]
Amylin	DMWDEN0	N. A.	N. A.	Phase 4	[14]
AMG 386	DMQJXL4	Breast cancer	2C60-2C65	Phase 3	[11]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[1]
PF-446687	DML38VU	Female sexual arousal dysfunction	HA01.1	Phase 2	[15]
AP-1030	DMBGA35	Metabolic disorder	5C50-5D2Z	Phase 1/2	[16]
PF-07258669	DM3CJ5N	Malnutrition	5B50-5B71	Phase 1	[17]
PT-14	DMYM9JL	Erectile dysfunction	HA01.1	Discontinued in 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	[19]
Mozavaptan	DMZ905C	Hyponatraemia	5C72	Approved	[20]
Oxytocin	DMDL27I	Autism spectrum disorder	6A02	Approved	[21]
Conivaptan	DM1V329	Euvolemic hyponatremia	5C72	Approved	[22]
Felypressin	DMHLP9C	Localisation	N.A.	Approved	[23]
Terlipressin	DMT9FH3	Hypertension	BA00-BA04	Approved	[24]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[25]
Balovaptan	DMKMTDG	Autism spectrum disorder	6A02	Phase 3	[26]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[1]
SSR149415	DMCMD93	Anxiety disorder	6B00-6B0Z	Phase 2	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Melanocortin receptor 4 (MC4R)	TTD0CIQ	MC4R_HUMAN	Inhibitor	[1]
Substance-K receptor (TACR2)	TTYO0A3	NK2R_HUMAN	Inhibitor	[1]
Vasopressin V1a receptor (V1AR)	TT4TFGN	V1AR_HUMAN	Inhibitor	[1]

References

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• [2] Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi. Eur J Pharmacol. 2013 Nov 15;720(1-3):180-5.
• [3] Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor. Eur J Pharmacol. 2005 Jun 1;516(2):104-11.
• [4] Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
• [5] Characterization of species-related differences in the pharmacology of tachykinin NK receptors 1, 2 and 3. Biochem Pharmacol. 2009 May 1;77(9):1522-30.
• [6] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [7] Effects of FK224, a novel compound NK1 and NK2 receptor antagonist, on airway constriction and airway edema induced by neurokinins and sensory nerv... J Pharmacol Exp Ther. 1992 Jul;262(1):403-8.
• [8] Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients. Eur Respir J. 2004 Jan;23(1):76-81.
• [9] Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma. Am J Respir Crit Care Med. 2007 Mar 1;175(5):450-7.
• [10] Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and human. Xenobiotica. 2000 Jun;30(6):627-42.
• [11] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [14] Novel anti-obesity drugs. Expert Opin Investig Drugs. 2000 Jun;9(6):1317-26.
• [15] Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole. Neuropsychopharmacology. 2015 Jul;40(8):1856-65.
• [16] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [17] Discovery of the Potent and Selective MC4R Antagonist PF-07258669 for the Potential Treatment of Appetite Loss. J Med Chem. 2023 Mar 9;66(5):3195-3211.
• [18] The protective effects of the melanocortin receptor (MCR) agonist, melanotan-II (MTII), against binge-like ethanol drinking are facilitated by deletion of the MC3 receptor in mice. Neuropeptides. 2014 Feb;48(1):47-51.
• [19] 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.
• [20] Nonpeptide vasopressin antagonists: a new group of hormone blockers entering the scene. Exp Clin Endocrinol Diabetes. 1999;107(3):157-65.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] Investigational vasopressin receptor modulators in the pipeline. Expert Opin Investig Drugs. 2009 Aug;18(8):1119-31.
• [25] The discovery of GSK221149A: a potent and selective oxytocin antagonist. Bioorg Med Chem Lett. 2008 Jan 1;18(1):90-4.
• [26] 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.
• [27] Tetrahydroquinoline sulfonamides as vasopressin 1b receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6018-22.