Rolapitant

Rolapitant, also known as SCH-619734, is an orally bioavailable, centrally-acting, selective, neurokinin 1 receptor (NK1-receptor) antagonist with potential antiemetic activity. Upon oral administration, rolapitant competitively binds to and blocks the activity of the NK1-receptor in the central nervous system, thereby inhibiting the binding of the endogenous ligand, substance P (SP). This may prevent both SP-induced emesis and chemotherapy-induced nausea and vomiting (CINV).

Product information

CAS Number: 552292-08-7

Molecular Weight: 500.48

Formula: C25H26F6N2O2

Chemical Name: Rolapitant

Smiles: C[C@@H](OC[C@]1(CC[C@@]2(CN1)CCC(=O)N2)C1C=CC=CC=1)C1C=C(C=C(C=1)C(F)(F)F)C(F)(F)F

InChiKey: FIVSJYGQAIEMOC-ZGNKEGEESA-N

InChi: InChI=1S/C25H26F6N2O2/c1-16(17-11-19(24(26,27)28)13-20(12-17)25(29,30)31)35-15-23(18-5-3-2-4-6-18)10-9-22(14-32-23)8-7-21(34)33-22/h2-6,11-13,16,32H,7-10,14-15H2,1H3,(H,33,34)/t16-,22-,23-/m1/s1

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Rolapitant has a high affinity for the human NK1 receptor with a Ki of 0.66 nM and high selectivity over the human NK2 and NK3 subtypes of more than 1000-fold, as well as preferential affinity for human, guinea pig, gerbil and monkey NK1 receptors over rat, mouse and rabbit.

In Vivo:

Rolapitant reverses NK1 agonist-induced foot tapping in gerbils following both intravenous and oral administration up to 24 hours at a minimal effective dose (MED) of 0.1 mg/kg. Rolapitant is active at 0.1 and 1 mg/kg in both acute and delayed emesis models in ferrets, respectively, consistent with clinical data for other NK1 antagonists. Clinical efficacy of anti-emetics is highly correlated with efficacy in the ferret emesis model, suggesting rolapitant is a viable clinical candidate for this indication.

References:

1. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548209/ PubMed PMID: 31643534.
2. Heo YA, Deeks ED. Rolapitant: A Review in Chemotherapy-Induced Nausea and Vomiting. Drugs. 2017 Oct;77(15):1687-1694. doi: 10.1007/s40265-017-0816-z. Review. PubMed PMID: 28929404.
3. Rapoport BL. Rolapitant: An NK-1 Receptor Antagonist for the Prevention of Chemotherapy- Induced Nausea and Vomiting. Rev Recent Clin Trials. 2017;12(3):193-201. doi: 10.2174/1574887112666170406104854. Review. PubMed PMID: 28393710.

Products are for research use only. Not for human use.