Netupitant

• CAT Number: A000038
• CAS Number: 290297-26-6
• Molecular Formula: C30H32F6N4O
• Molecular Weight: 578.59
• Purity: ≥95%
• Target: Substance P/NK1 Receptor
• Solubility: Soluble in DMSO
• Storage: Store at -20°C
• InChI: 1S/C30H32F6N4O/c1-19-8-6-7-9-23(19)24-17-26(40-12-10-38(4)11-13-40)37-18-25(24)39(5)27(41)28(2,3)20-14-21(29(31,32)33)16-22(15-20)30(34,35)36/h6-9,14-18H,10-13H2,1-5H3
• InChIKey: WAXQNWCZJDTGBU-UHFFFAOYSA-N
• SMILES: CC1=CC=CC=C1C2=CC(=NC=C2N(C)C(=O)C(C)(C)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)N4CCN(CC4)C

Netupitant is a selective neurokinin 1 (NK1) receptor antagonist with potential antiemetic activity. Netupitant competitively binds to and blocks the activity of the human substance P/NK1 receptors in the central nervous system (CNS), thereby inhibiting NK1-receptor binding of the endogenous tachykinin neuropeptide substance P (SP), which may result in the prevention of chemotherapy-induced nausea and vomiting (CINV). SP is found in neurons of vagal afferent fibers innervating the brain-stem nucleus tractus solitarii and the area postrema, which contains the chemoreceptor trigger zone (CTZ), and may be elevated in response to chemotherapy. The NK-receptor is a G-protein receptor coupled to the inositol phosphate signal-transduction pathway and is found in both the nucleus tractus solitarii and the area postrema. Check for active clinical trials or closed clinical trials using this agent. O n 10/10 2014 FDA approved netupitant for the treatment of nausea and vomiting in patients undergoing cancer chemotherapy.

Reference

1: Zhang L, Lu S, Feng J, Dechaphunkul A, Chang J, Wang D, Chessari S, Lanzarotti
C, Jordan K, Aapro M. A Randomized Phase 3 Study Evaluating the Efficacy of
Single-dose NEPA, a Fixed Antiemetic Combination of Netupitant and Palonosetron,
Versus an Aprepitant Regimen for Prevention of Chemotherapy-induced Nausea and
Vomiting (CINV) in Patients Receiving Highly Emetogenic Chemotherapy (HEC). Ann
Oncol. 2017 Oct 28. doi: 10.1093/annonc/mdx698. [Epub ahead of print] PubMed
PMID: 29092012.

2: Hesketh PJ, Palmas M, Nicolas P. Preventing chemotherapy-induced nausea and
vomiting in patients with lung cancer: efficacy of NEPA
(netupitant-palonosetron), the first combination antiemetic. Support Care Cancer.
2017 Oct 28. doi: 10.1007/s00520-017-3936-9. [Epub ahead of print] PubMed PMID:
29080920.

3: Cawston H, Bourhis F, Eriksson J, Ruffo P, D/’Agostino P, Turini M,
Schwartzberg L, McGuire A. NEPA, a new fixed combination of netupitant and
palonosetron, is a cost-effective intervention for the prevention of
chemotherapy-induced nausea and vomiting in the UK. Drugs Context. 2017 Mar
24;6:212298. doi: 10.7573/dic.212298. eCollection 2017. Review. PubMed PMID:
28392826; PubMed Central PMCID: PMC5378057.

4: Rugo HS, Rossi G, Rizzi G, Aapro M. Efficacy of NEPA (netupitant/palonosetron)
across multiple cycles of chemotherapy in breast cancer patients: A subanalysis
from two phase III trials. Breast. 2017 Jun;33:76-82. doi:
10.1016/j.breast.2017.02.017. Epub 2017 Mar 10. PubMed PMID: 28285236.

5: Aapro M, Jordan K, Gralla RJ, Rizzi G, Rossi G, Palmas M, Alyasova AV,
Lisyanskaya AS, Bošnjak SM, Hesketh PJ. Safety and efficacy of NEPA, an oral
fixed combination of netupitant and palonosetron, in older patients. J Geriatr
Oncol. 2017 Jan;8(1):56-63. doi: 10.1016/j.jgo.2016.09.002. Epub 2016 Nov 23.
PubMed PMID: 27889278.

6: Aapro M, Karthaus M, Schwartzberg L, Bondarenko I, Sarosiek T, Oprean C,
Cardona-Huerta S, Hansen V, Rossi G, Rizzi G, Borroni ME, Rugo H. NEPA, a fixed
oral combination of netupitant and palonosetron, improves control of
chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of
chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral
palonosetron. Support Care Cancer. 2017 Apr;25(4):1127-1135. doi:
10.1007/s00520-016-3502-x. Epub 2016 Nov 24. PubMed PMID: 27885469; PubMed
Central PMCID: PMC5321708.

7: Coyne JW. The First Oral Fixed-Dose Combination of Netupitant and Palonosetron
for the Treatment of Chemotherapy-Induced Nausea and Vomiting. J Adv Pract Oncol.
2016 Jan-Feb;7(1):66-70. Epub 2016 Jan 1. Review. PubMed PMID: 27713845; PubMed
Central PMCID: PMC5045279.