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

General Information of Drug (ID: DM4ZO01)

• Drug Name: DNK-333 Drug Info
• Synonyms: DNK 333; DNK333; N-((R,R)-(E)-1-(3,4-Dichlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl)allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide

Indication

Disease Entry	ICD 11	Status	REF
Irritable bowel syndrome	DD91.0	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 9939040
  CAS Number: CAS 398507-81-8
  TTD Drug ID: DM4ZO01

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[3]
Selegiline	DM6034S	Major depressive disorder	6A70.3	Approved	[4]
Rolapitant	DM8XP26	Chemotherapy-induced nausea	MD90	Approved	[5]
Netupitant	DMEKAYI	Chemotherapy-induced nausea	MD90	Phase 3	[5]
Serlopitant	DM5VH6U	Prurigo nodularis	EC91.0	Phase 3	[6]
LY-686017	DM7WORZ	Atopic dermatitis	EA80	Phase 3	[7]
Elinzanetant	DMC6EFI	Hot flushes	GA30	Phase 3	[8]
CP-122721	DMSWLM5	Major depressive disorder	6A70.3	Phase 2	[9]
FR139317	DMEL5SV	Hypertension	BA00-BA04	Phase 2	[4]
VOFOPITANT HYDROCHLORIDE	DMQMYP5	Vomiting	MD90	Phase 2	[10]

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	[11]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[12]
Rambazole	DMP2DNS	Psoriasis vulgaris	EA90	Phase 2	[13]
Nepadutant	DMPMF6L	Infantile colics	DD93.1	Phase 1/2	[14]
Saredutant	DMSRJY3	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[15]
CS-003	DM1AEVT	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[1]
FK-224	DM1JUS0	Asthma	CA23	Discontinued in Phase 2	[16]
AVE-5883	DM3P84V	Asthma	CA23	Discontinued in Phase 1/2	[17]
UK-224671	DMDTRJB	Urinary incontinence	MF50.2	Discontinued in Phase 1	[18]
SR 144190	DMK4XT8	Acute or chronic pain	MG30-MG31	Discontinued in Phase 1	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Substance-K receptor (TACR2)	TTYO0A3	NK2R_HUMAN	Modulator	[2]
Substance-P receptor (TACR1)	TTZPO1L	NK1R_HUMAN	Modulator	[2]

References

• [1] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [2] Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients. Eur Respir J. 2004 Jan;23(1):76-81.
• [3] Potent, brain-penetrant, hydroisoindoline-based human neurokinin-1 receptor antagonists. J Med Chem. 2009 May 14;52(9):3039-46.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [5] Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Stress-related neuropeptides and alcoholism: CRH, NPY and beyond. Alcohol. 2009 November; 43(7): 491-498.
• [8] 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.
• [9] A review of drug options in age-related macular degeneration therapy and potential new agents. Expert Opin Pharmacother. 2006 Dec;7(17):2355-68.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and human. Xenobiotica. 2000 Jun;30(6):627-42.
• [19] Pharmacologic evaluation of neurokinin-2 receptor antagonists in the guinea pig respiratory tract. Am J Vet Res. 2004 Jul;65(7):984-91.