WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205981
CAS#: 290297-26-6 (free base)
Description: 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).
Hodoodo Cat#: H205981
Name: Netupitant
CAS#: 290297-26-6 (free base)
Chemical Formula: C30H32F6N4O
Exact Mass: 578.25
Molecular Weight: 578.590
Elemental Analysis: C, 62.28; H, 5.57; F, 19.70; N, 9.68; O, 2.77
Related CAS #: 290296-54-7 (2HCl) 290297-26-6 (free base)
Synonym: AGE94200; AGE-94200; AGE 94200;Ro 67-3189; Ro-67-3189; Ro67-3189; Ro 67-3189/000; Netupitant.
IUPAC/Chemical Name: 2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethyl-N-(6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-yl)propanamide
InChi Key: WAXQNWCZJDTGBU-UHFFFAOYSA-N
InChi Code: 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
SMILES Code: CC(C)(C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1)C(N(C)C2=C(C3=CC=CC=C3C)C=C(N4CCN(C)CC4)N=C2)=O
Appearance: White solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: 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.
| Biological target: | Netupitant (CID-6451149) is a neurokinin-1 (NK1) receptor antagonist with a Ki of 0.95 nM for hNK1 in CHO cells. |
| In vitro activity: | TBD |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 2.0 | 3.50 |
The following data is based on the product molecular weight 578.59 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Rudd JA, Ngan MP, Lu Z, Higgins GA, Giuliano C, Lovati E, Pietra C. Profile of Antiemetic Activity of Netupitant Alone or in Combination with Palonosetron and Dexamethasone in Ferrets and Suncus murinus (House Musk Shrew). Front Pharmacol. 2016 Aug 31;7:263. doi: 10.3389/fphar.2016.00263. PMID: 27630563; PMCID: PMC5005416. 2. Palea S, Guilloteau V, Rekik M, Lovati E, Guerard M, Guardia MA, Lluel P, Pietra C, Yoshiyama M. Netupitant, a Potent and Highly Selective NK1 Receptor Antagonist, Alleviates Acetic Acid-Induced Bladder Overactivity in Anesthetized Guinea-Pigs. Front Pharmacol. 2016 Aug 4;7:234. doi: 10.3389/fphar.2016.00234. PMID: 27540361; PMCID: PMC4972833. |
| In vitro protocol: | TBD |
| In vivo protocol: | 1. Rudd JA, Ngan MP, Lu Z, Higgins GA, Giuliano C, Lovati E, Pietra C. Profile of Antiemetic Activity of Netupitant Alone or in Combination with Palonosetron and Dexamethasone in Ferrets and Suncus murinus (House Musk Shrew). Front Pharmacol. 2016 Aug 31;7:263. doi: 10.3389/fphar.2016.00263. PMID: 27630563; PMCID: PMC5005416. 2. Palea S, Guilloteau V, Rekik M, Lovati E, Guerard M, Guardia MA, Lluel P, Pietra C, Yoshiyama M. Netupitant, a Potent and Highly Selective NK1 Receptor Antagonist, Alleviates Acetic Acid-Induced Bladder Overactivity in Anesthetized Guinea-Pigs. Front Pharmacol. 2016 Aug 4;7:234. doi: 10.3389/fphar.2016.00234. PMID: 27540361; PMCID: PMC4972833. |
1: Lorusso V, Karthaus M, Aapro M. Review of oral fixed-dose combination netupitant and palonosetron (NEPA) for the treatment of chemotherapy-induced nausea and vomiting. Future Oncol. 2014 Oct 31:1-13. [Epub ahead of print] PubMed PMID: 25360998.
2: Spinelli T, Moresino C, Baumann S, Timmer W, Schultz A. Effects of combined netupitant and palonosetron (NEPA), a cancer supportive care antiemetic, on the ECG of healthy subjects: an ICH E14 thorough QT trial. Springerplus. 2014 Jul 29;3:389. doi: 10.1186/2193-1801-3-389. eCollection 2014. PubMed PMID: 25105088; PubMed Central PMCID: PMC4124105.
3: Thomas AG, Stathis M, Rojas C, Slusher BS. Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44. doi: 10.1007/s00221-014-4017-7. Epub 2014 Jun 27. PubMed PMID: 24969614; PubMed Central PMCID: PMC4112047.
4: Andrews PL. Netupitant and palonosetron (NEPA): a winning team in the race for the optimal treatment of chemotherapy-induced nausea and vomiting? Ann Oncol. 2014 Jul;25(7):1258-9. doi: 10.1093/annonc/mdu190. Epub 2014 Jun 18. PubMed PMID: 24942276.
5: Gralla RJ, Bosnjak SM, Hontsa A, Balser C, Rizzi G, Rossi G, Borroni ME, Jordan K. A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy. Ann Oncol. 2014 Jul;25(7):1333-9. doi: 10.1093/annonc/mdu096. Epub 2014 Mar 14. PubMed PMID: 24631949; PubMed Central PMCID: PMC4071753.
6: Hesketh PJ, Rossi G, Rizzi G, Palmas M, Alyasova A, Bondarenko I, Lisyanskaya A, Gralla RJ. Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study. Ann Oncol. 2014 Jul;25(7):1340-6. doi: 10.1093/annonc/mdu110. Epub 2014 Mar 7. PubMed PMID: 24608196; PubMed Central PMCID: PMC4071755.
7: Aapro M, Rugo H, Rossi G, Rizzi G, Borroni ME, Bondarenko I, Sarosiek T, Oprean C, Cardona-Huerta S, Lorusso V, Karthaus M, Schwartzberg L, Grunberg S. A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol. 2014 Jul;25(7):1328-33. doi: 10.1093/annonc/mdu101. Epub 2014 Mar 5. PubMed PMID: 24603643; PubMed Central PMCID: PMC4071754.
8: Szitter I, Pintér E, Perkecz A, Kemény A, Kun J, Kereskai L, Pietra C, Quinn JP, Zimmer A, Berger A, Paige CJ, Helyes Z. Role of neurokinin 1 receptors in dextran sulfate-induced colitis: studies with gene-deleted mice and the selective receptor antagonist netupitant. Inflamm Res. 2014 May;63(5):399-409. doi: 10.1007/s00011-014-0712-x. Epub 2014 Jan 28. PubMed PMID: 24468892.
9: Spinelli T, Calcagnile S, Giuliano C, Rossi G, Lanzarotti C, Mair S, Stevens L, Nisbet I. Netupitant PET imaging and ADME studies in humans. J Clin Pharmacol. 2014 Jan;54(1):97-108. doi: 10.1002/jcph.198. Epub 2013 Nov 8. PubMed PMID: 24122871.
10: Haab F, Braticevici B, Krivoborodov G, Palmas M, Zufferli Russo M, Pietra C. Efficacy and safety of repeated dosing of netupitant, a neurokinin-1 receptor antagonist, in treating overactive bladder. Neurourol Urodyn. 2014 Mar;33(3):335-40. doi: 10.1002/nau.22406. Epub 2013 Jun 14. PubMed PMID: 23765630.
