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

General Information of Drug (ID: DMK2PBD)

• Drug Name: Palonosetron + fosnetupitant Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Chemotherapy-induced nausea	MD90	Approved	[1]

• Cross-matching ID: TTD Drug ID: DMK2PBD

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	[2]
Selegiline	DM6034S	Major depressive disorder	6A70.3	Approved	[3]
Rolapitant	DM8XP26	Chemotherapy-induced nausea	MD90	Approved	[4]
Netupitant	DMEKAYI	Chemotherapy-induced nausea	MD90	Phase 3	[4]
Serlopitant	DM5VH6U	Prurigo nodularis	EC91.0	Phase 3	[5]
LY-686017	DM7WORZ	Atopic dermatitis	EA80	Phase 3	[6]
CP-122721	DMSWLM5	Major depressive disorder	6A70.3	Phase 2	[7]
FR139317	DMEL5SV	Hypertension	BA00-BA04	Phase 2	[3]
VOFOPITANT HYDROCHLORIDE	DMQMYP5	Vomiting	MD90	Phase 2	[8]
LY-2590443	DM81UJW	Migraine	8A80	Phase 2	[9]

Drug(s) Targeting 5-HT 3A receptor (HTR3A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dolasetron	DMMG26Z	Nausea	MD90	Approved	[10]
Alosetron	DML2A03	Irritable bowel syndrome	DD91.0	Approved	[11]
Tropisetron	DMNSJ7V	Fibromyalgia	MG30.01	Approved	[12]
Palonosetron	DMBHMOX	Nausea	MD90	Approved	[13]
Levetiracetam	DMTGDN8	Epilepsy	8A60-8A68	Approved	[12]
Procaine	DM4LSNE	Anaesthesia	9A78.6	Approved	[14]
Cilansetron	DMP0NGX	Irritable bowel syndrome	DD91.0	Phase 3	[15]
BEMESETRON	DMSPJX9	N. A.	N. A.	Discontinued in Phase 3	[16]
Norcisapride	DMJSKUI	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[17]
YM-114	DML2IXO	Nausea	MD90	Discontinued in Phase 2	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Antagonist	[1]
Substance-P receptor (TACR1)	TTZPO1L	NK1R_HUMAN	Antagonist	[1]

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [2] Potent, brain-penetrant, hydroisoindoline-based human neurokinin-1 receptor antagonists. J Med Chem. 2009 May 14;52(9):3039-46.
• [3] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [4] Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Stress-related neuropeptides and alcoholism: CRH, NPY and beyond. Alcohol. 2009 November; 43(7): 491-498.
• [7] A review of drug options in age-related macular degeneration therapy and potential new agents. Expert Opin Pharmacother. 2006 Dec;7(17):2355-68.
• [8] 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.
• [9] 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. (Target id: 360).
• [10] Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, do... Lancet Oncol. 2009 Feb;10(2):115-24.
• [11] Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009 Jul;104(7):1831-43; quiz 1844.
• [12] Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
• [13] Management of postoperative nausea and vomiting: focus on palonosetron. Ther Clin Risk Manag. 2009 Feb;5(1):21-34.
• [14] Local anesthetics have different mechanisms and sites of action at recombinant 5-HT3 receptors. Reg Anesth Pain Med. 2007 Nov-Dec;32(6):462-70.
• [15] Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea.Expert Opin Investig Drugs.2005 Feb;14(2):185-93.
• [16] Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships. J Med Chem. 1992 Jan 24;35(2):310-9.
• [17] mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I). Bioorg Med Chem Lett. 2009 Oct 1;19(19):5679-83.
• [18] Effect of serotonin (5-HT)3-receptor antagonists YM060, YM114 (KAE-393), ondansetron and granisetron on 5-HT4 receptors and gastric emptying in rodents. Jpn J Pharmacol. 1995 Nov;69(3):205-14.