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

General Information of Drug (ID: DMK3S9J)

• Drug Name: GSK1144814 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Alcohol dependence	6C40.2	Phase 1	[1]
Schizophrenia	6A20	Phase 1	[2]

• Cross-matching ID: TTD Drug ID: DMK3S9J

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	[4]
Elinzanetant	DMC6EFI	Hot flushes	GA30	Phase 3	[5]
Senktide	DMOH8LD	Epilepsy	8A60-8A68	Phase 2	[6]
AZD2624	DMZLGQV	Multiple sclerosis	8A40	Phase 2	[7]
Talnetant	DMQKZDT	Schizophrenia	6A20	Phase 2	[8]
Osanetant	DMMT4PB	Schizoaffective disorder	6A21	Discontinued in Phase 2b	[8]
CS-003	DM1AEVT	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[9]
SSR-146977	DMR9JA8	Psychotic disorder	6A20-6A25	Discontinued in Phase 1	[10]
SB222200	DM6X0PZ	Schizoaffective disorder	6A21	Preclinical	[11]
neurokinin A	DM9UXRP	Discovery agent	N.A.	Investigative	[12]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[13]
Selegiline	DM6034S	Major depressive disorder	6A70.3	Approved	[14]
Rolapitant	DM8XP26	Chemotherapy-induced nausea	MD90	Approved	[15]
Netupitant	DMEKAYI	Chemotherapy-induced nausea	MD90	Phase 3	[15]
Serlopitant	DM5VH6U	Prurigo nodularis	EC91.0	Phase 3	[16]
LY-686017	DM7WORZ	Atopic dermatitis	EA80	Phase 3	[17]
Elinzanetant	DMC6EFI	Hot flushes	GA30	Phase 3	[5]
CP-122721	DMSWLM5	Major depressive disorder	6A70.3	Phase 2	[18]
FR139317	DMEL5SV	Hypertension	BA00-BA04	Phase 2	[14]
VOFOPITANT HYDROCHLORIDE	DMQMYP5	Vomiting	MD90	Phase 2	[19]

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	Modulator	[3]
Substance-P receptor (TACR1)	TTZPO1L	NK1R_HUMAN	Modulator	[3]

References

• [1] ClinicalTrials.gov (NCT01181908) Alcohol Interaction Study. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT01090440) Pharmacokinetics, Effect of Food, Safety and Tolerability of a New Tablet Formulation of GSK1144814 in Healthy Subjects (MNK112891) in GlaxoSmithKline.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Pharmacological characterization of senktide-induced tail whips. Neuropharmacology. 2010 Jan;58(1):259-67.
• [9] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [10] 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.
• [11] 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.
• [12] Molecular and pharmacological characterization of the murine tachykinin NK(3) receptor. Eur J Pharmacol. 2001 Feb 16;413(2-3):143-50.
• [13] Potent, brain-penetrant, hydroisoindoline-based human neurokinin-1 receptor antagonists. J Med Chem. 2009 May 14;52(9):3039-46.
• [14] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [15] Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44.
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Stress-related neuropeptides and alcoholism: CRH, NPY and beyond. Alcohol. 2009 November; 43(7): 491-498.
• [18] A review of drug options in age-related macular degeneration therapy and potential new agents. Expert Opin Pharmacother. 2006 Dec;7(17):2355-68.
• [19] 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.