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

General Information of Drug (ID: DM9UXRP)

• Drug Name: neurokinin A Drug Info
• Synonyms: substance K

Indication

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

• Cross-matching ID:
  PubChem CID: 5311311
  CAS Number: CAS 86933-74-6
  TTD Drug ID: DM9UXRP

Molecule-Related Drug Atlas

Drug(s) Targeting Neuromedin-K receptor (TACR3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fezolinetant	DMHDQZD	Hot flushes	GA30	Approved	[6]
Elinzanetant	DMC6EFI	Hot flushes	GA30	Phase 3	[7]
Senktide	DMOH8LD	Epilepsy	8A60-8A68	Phase 2	[8]
AZD2624	DMZLGQV	Multiple sclerosis	8A40	Phase 2	[9]
Talnetant	DMQKZDT	Schizophrenia	6A20	Phase 2	[10]
GSK1144814	DMK3S9J	Alcohol dependence	6C40.2	Phase 1	[11]
Osanetant	DMMT4PB	Schizoaffective disorder	6A21	Discontinued in Phase 2b	[10]
CS-003	DM1AEVT	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[12]
SSR-146977	DMR9JA8	Psychotic disorder	6A20-6A25	Discontinued in Phase 1	[13]
SB222200	DM6X0PZ	Schizoaffective disorder	6A21	Preclinical	[14]

Drug(s) Targeting Substance-P receptor (TACR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[15]
Selegiline	DM6034S	Major depressive disorder	6A70.3	Approved	[16]
Rolapitant	DM8XP26	Chemotherapy-induced nausea	MD90	Approved	[17]
Netupitant	DMEKAYI	Chemotherapy-induced nausea	MD90	Phase 3	[17]
Serlopitant	DM5VH6U	Prurigo nodularis	EC91.0	Phase 3	[18]
LY-686017	DM7WORZ	Atopic dermatitis	EA80	Phase 3	[19]
Elinzanetant	DMC6EFI	Hot flushes	GA30	Phase 3	[7]
CP-122721	DMSWLM5	Major depressive disorder	6A70.3	Phase 2	[20]
FR139317	DMEL5SV	Hypertension	BA00-BA04	Phase 2	[16]
VOFOPITANT HYDROCHLORIDE	DMQMYP5	Vomiting	MD90	Phase 2	[21]

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	[22]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[23]
Rambazole	DMP2DNS	Psoriasis vulgaris	EA90	Phase 2	[5]
Nepadutant	DMPMF6L	Infantile colics	DD93.1	Phase 1/2	[24]
Saredutant	DMSRJY3	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[25]
CS-003	DM1AEVT	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[12]
FK-224	DM1JUS0	Asthma	CA23	Discontinued in Phase 2	[26]
DNK-333	DM4ZO01	Irritable bowel syndrome	DD91.0	Discontinued in Phase 2	[27]
AVE-5883	DM3P84V	Asthma	CA23	Discontinued in Phase 1/2	[28]
UK-224671	DMDTRJB	Urinary incontinence	MF50.2	Discontinued in Phase 1	[29]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[30]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[31]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[32]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[33]
Saredutant	DMSRJY3	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[5]
bisphenol A	DM2ZLD7	Discovery agent	N.A.	Investigative	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Neuromedin-K receptor (TACR3)	TTBPGLU	NK3R_HUMAN	Agonist	[2]
Substance-K receptor (TACR2)	TTYO0A3	NK2R_HUMAN	Agonist	[3]
Substance-P receptor (TACR1)	TTZPO1L	NK1R_HUMAN	Agonist	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Substance-K receptor (TACR2)	OTTQHQZM	NK2R_HUMAN	Protein Interaction/Cellular Processes	[5]

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: 2089).
• [2] Molecular and pharmacological characterization of the murine tachykinin NK(3) receptor. Eur J Pharmacol. 2001 Feb 16;413(2-3):143-50.
• [3] Structure-activity relationships of neurokinin A (4-10) at the human tachykinin NK(2) receptor: the role of natural residues and their chirality. Biochem Pharmacol. 2001 Jan 1;61(1):55-60.
• [4] Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist. J Pharmacol Exp Ther.1997 Jun;281(3):1303-11.
• [5] 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.
• [6] Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023 Apr 1;401(10382):1091-1102.
• [7] Elinzanetant (NT-814), a Neurokinin 1,3 Receptor Antagonist, Reduces Estradiol and Progesterone in Healthy Women. J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3221-e3234.
• [8] Implication of nigral tachykinin NK3 receptors in the maintenance of hypertension in spontaneously hypertensive rats: a pharmacologic and autoradiographic study. Br J Pharmacol. 2003 Feb;138(4):554-63.
• [9] The selective neurokinin 3 antagonist AZD2624 does not improve symptoms or cognition in schizophrenia: a proof-of-principle study.J Clin Psychopharmacol.2014 Apr;34(2):199-204.
• [10] Pharmacological characterization of senktide-induced tail whips. Neuropharmacology. 2010 Jan;58(1):259-67.
• [11] Pharmacokinetics and central nervous system effects of the novel dual NK1 /NK3 receptor antagonist GSK1144814 in alcohol-intoxicated volunteers.Br J Clin Pharmacol.2013 May;75(5):1328-39.
• [12] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [13] Biochemical and pharmacological activities of SSR 146977, a new potent nonpeptide tachykinin NK3 receptor antagonist. Can J Physiol Pharmacol. 2002 May;80(5):482-8.
• [14] Evidence for mediation of nociception by injection of the NK-3 receptor agonist, senktide, into the dorsal periaqueductal gray of rats. Psychopharmacology (Berl). 2009 May;204(1):13-24.
• [15] Potent, brain-penetrant, hydroisoindoline-based human neurokinin-1 receptor antagonists. J Med Chem. 2009 May 14;52(9):3039-46.
• [16] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [17] Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44.
• [18] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [19] Stress-related neuropeptides and alcoholism: CRH, NPY and beyond. Alcohol. 2009 November; 43(7): 491-498.
• [20] A review of drug options in age-related macular degeneration therapy and potential new agents. Expert Opin Pharmacother. 2006 Dec;7(17):2355-68.
• [21] Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenicchemotherapy: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jun;10(6):549-58.
• [22] 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.
• [23] 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.
• [24] Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
• [25] 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.
• [26] 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.
• [27] Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients. Eur Respir J. 2004 Jan;23(1):76-81.
• [28] 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.
• [29] Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and human. Xenobiotica. 2000 Jun;30(6):627-42.
• [30] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [31] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [32] Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough. Thorax. 2006 Dec;61(12):1070-5. doi: 10.1136/thx.2005.054429. Epub 2006 Aug 7.
• [33] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [34] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.