Rolapitant

SKU: orb1223100

Description

Rolapitant Hydrochloride is the hydrochloride salt form of rolapitant, 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). The interaction of SP with the NK1-receptor plays a key role in the induction of nausea and vomiting caused by emetogenic cancer chemotherapy. Compared to other NK1-receptor antagonists, rolapitant has both a more rapid onset of action and a much longer half-life.

Key Properties

• CAS Number: 552292-08-7
• MW: 500.48
• Purity: >98% (HPLC)
• Formula: C₂₅H₂₆F₆N₂O₂
• SMILES: C[C@H](c1cc(cc(c1)C(F)(F)F)C(F)(F)F)OC[C@]1(CC[C@]2(CCC(=O)N2)CN1)c1ccccc1
• Target: NK1
• Solubility: DMSO : ≥ 30 mg/mL; 59.94 mM

Bioactivity

• In Vivo:
  Rolapitant (0.03-1 mg/kg for PO, 0.3-1 mg/kg for IV; single dosage) attenuates the GR-73632-induced foot-tapping response in Mongolian Gerbils. Rolapitant (0.03-1 mg/kg; PO; single dosage; observed for 72 h) blocks acute emesis induced by both apomorphine and cisplatin in ferrets. Animal model: Female Mongolian Gerbils (30-60 g; anesthetized by inhalation of an oxygen: isofluorane mixture after 4 h PO or immediately after IV, then injected with 5 μl of 3 pmol solution of GR-73632 via ICV). Dosage: 0.03, 0.1, 0.3 and 1 mg/kg for PO, 0.3 and 1 mg/kg for IV. Administration: PO or IV, single dosage. Result: Attenuated dose-dependently the GR-73632-induced foot-tapping response when administered PO 4 h before testing, with an ID90 of 0.3 mg/kg, and the inhibition in foot tapping for at least 24 h. Blocked dose-dependently the foot tapping induced by GR-73632 when administered IV, with complete blockade observed at 1 mg/kg. Animal model: Ferrets (treated with subcutaneous administration of 0.125 mg/kg apomorphine or intraperitoneal administration of 10 mg/kg cisplatin). Dosage: 0.03, 0.1, 0.3 and 1 mg/kg. Administration: PO; single dosage; observed for 72 h. Result: Blocked dose-dependently acute emesis induced by both apomorphine and cisplatin in ferrets. Produced a robust decrease in retches and vomits in ferrets that was maintained throughout the 72 h observation period.
• In Vitro:
  Rolapitant has 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. Rolapitant (1-1000 nM) inhibits the GR-73632 (an NK1 receptor agonist)-induced calcium efflux with a concentration-dependent and competitive manner in CHO cells expressing the human NK1 receptor.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SCH619734

Quick Database Links

Gene Symbol

NK1