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

General Information of Drug (ID: DMJ14NE)

• Drug Name: WAY-207024 Drug Info
• Synonyms: WAY-207024; CHEMBL474991; 872002-72-7; GTPL5582; SCHEMBL3275225; SCHEMBL13324654; BDBM50256882; ZINC35923465; WAY 207024; NCGC00370941-01; KB-81482; 6-((4-(2-(4-tert-butylphenyl)-1H-benzo[d]imidazol-4-yl)piperazin-1-yl)methyl)quinoxaline

Indication

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

• Cross-matching ID:
  PubChem CID: 11496610
  TTD Drug ID: DMJ14NE

Molecule-Related Drug Atlas

Drug(s) Targeting Gonadotropin-releasing hormone receptor (GNRHR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gonadorelin	DMAQ469	Amenorrhea	GA20.0	Approved	[4]
Relugolix	DMK7IWL	Prostate cancer	2C82.0	Approved	[5]
Ganirelix	DMGMB30	Ovulation dysfunction	5A80	Approved	[6]
Abarelix	DM5WFNP	Prostate cancer	2C82.0	Approved	[7]
Triptorelin	DMTK4LS	Infertility	GB04	Approved	[8]
Leuprorelin acetate	DM15HAT	Prostate cancer	2C82.0	Approved	[9]
Nafarelin	DMAHEFY	Endometriosis	GA10	Approved	[10]
Cetrorelix	DMFD9Q6	Ovarian stimulation	LB45.1	Approved	[11]
Elagolix sodium	DMRDUC0	Endometriosis	GA10	Approved	[12]
Degarelix	DM3O8QY	Prostate cancer	2C82.0	Approved	[13]

Drug(s) Targeting Histamine H2 receptor (H2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[14]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[15]
Famotidine	DMRL3AB	Gastric ulcer	DA60	Approved	[15]
Nizatidine	DMGFV3Z	Acid-reflux disorder	DA22	Approved	[16]
Betazole	DMUFGAY	Gastric secretory disorder	DD90	Approved	[17]
Ebrotidine	DMV5KR3	Duodenal ulcer	DA63	Withdrawn from market	[18]
Pibutidine	DMXSTRM	Ulcerative colitis	DD71	Discontinued in Phase 3	[19]
Osutidine	DMN7TL8	Duodenal ulcer	DA63	Discontinued in Phase 3	[20]
KU-1257	DMZMFX6	Duodenal ulcer	DA63	Discontinued in Phase 3	[21]
Lavoltidine	DMTY5VE	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[22]

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	[23]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[24]
Rambazole	DMP2DNS	Psoriasis vulgaris	EA90	Phase 2	[25]
Nepadutant	DMPMF6L	Infantile colics	DD93.1	Phase 1/2	[26]
Saredutant	DMSRJY3	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[27]
CS-003	DM1AEVT	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[28]
FK-224	DM1JUS0	Asthma	CA23	Discontinued in Phase 2	[29]
DNK-333	DM4ZO01	Irritable bowel syndrome	DD91.0	Discontinued in Phase 2	[30]
AVE-5883	DM3P84V	Asthma	CA23	Discontinued in Phase 1/2	[31]
UK-224671	DMDTRJB	Urinary incontinence	MF50.2	Discontinued in Phase 1	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Gonadotropin-releasing hormone receptor (GNRHR)	TT8R70G	GNRHR_HUMAN	Inhibitor	[2]
Histamine H2 receptor (H2R)	TTQHJ1K	HRH2_HUMAN	Inhibitor	[3]
Substance-K receptor (TACR2)	TTYO0A3	NK2R_HUMAN	Inhibitor	[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: 5582).
• [2] Synthesis and biological evaluation of piperazinyl heterocyclic antagonists of the gonadotropin releasing hormone (GnRH) receptor. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2512-5.
• [3] Discovery of 6-({4-[2-(4-tert-butylphenyl)-1H-benzimidazol-4-yl]piperazin-1-yl}methyl)quinoxaline (WAY-207024): an orally active antagonist of the ... J Med Chem. 2009 Apr 9;52(7):2148-52.
• [4] Use of cognitive behavior therapy for functional hypothalamic amenorrhea. Ann N Y Acad Sci. 2006 Dec;1092:114-29.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [6] Age attenuates testosterone secretion driven by amplitude-varying pulses of recombinant human luteinizing hormone during acute gonadotrope inhibiti... J Clin Endocrinol Metab. 2007 Sep;92(9):3626-32.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Regulation of GnRH I receptor gene expression by the GnRH agonist triptorelin, estradiol, and progesterone in the gonadotroph-derived cell line alphaT3-1. Endocrine. 2006 Aug;30(1):139-44.
• [9] Clinical pipeline report, company report or official report of Takeda (2009).
• [10] Reversible downregulation of endocrine and germinative testicular function (hormonal castration) in the dog with the GnRH-agonist azagly-nafarelin ... Theriogenology. 2009 Apr 15;71(7):1037-45.
• [11] Gonadotropin releasing hormone analogs induce apoptosis by extrinsic pathway involving p53 phosphorylation in primary cell cultures of human prostatic adenocarcinomas. Prostate. 2009 Jul 1;69(10):1025-33.
• [12] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [13] Iterative approach to the discovery of novel degarelix analogues: substitutions at positions 3, 7, and 8. Part II. J Med Chem. 2005 Jul 28;48(15):4851-60.
• [14] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [15] Histamine H1 and H2 receptor antagonists accelerate skin barrier repair and prevent epidermal hyperplasia induced by barrier disruption in a dry environment. J Invest Dermatol. 2001 Feb;116(2):261-5.
• [16] Does the use of nizatidine, as a pro-kinetic agent, improve gastric emptying in patients post-oesophagectomy J Gastrointest Surg. 2009 Mar;13(3):432-7.
• [17] Effect of nizatidine and cimetidine on betazole-stimulated gastric secretion of normal subjects: comparison of effects on acid, water, and pepsin. Am J Gastroenterol. 1988 Jan;83(1):32-6.
• [18] Histamine H2-receptor antagonist action of ebrotidine. Effects on gastric acid secretion, gastrin levels and NSAID-induced gastrotoxicity in the rat. Arzneimittelforschung. 1997 Apr;47(4A):439-46.
• [19] Comparative pharmacology of epibatidine: a potent agonist for neuronal nicotinic acetylcholine receptors. Mol Pharmacol. 1995 Oct;48(4):774-82.
• [20] Effects of osutidine (T-593) and its enantiomers on gastric mucosal hemodynamics and mucosal integrity in anesthetized rats. Arzneimittelforschung. 2001 Jan;51(1):46-50.
• [21] Pharmacological profiles of the new histamine H2-receptor antagonist N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy] propyl] urea. Arzneimittelforschung. 1993 Feb;43(2):129-33.
• [22] New and Future Drug Development for Gastroesophageal Reflux Disease. J Neurogastroenterol Motil. 2014 January; 20(1): 6-16.
• [23] 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.
• [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] 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.
• [26] Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
• [27] 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.
• [28] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [29] 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.
• [30] Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients. Eur Respir J. 2004 Jan;23(1):76-81.
• [31] 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.
• [32] Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and human. Xenobiotica. 2000 Jun;30(6):627-42.