Rolapitant

Research use only, not for human use.

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.

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.

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.

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.

SCH619734

Others

Other Targets

NK1

Cancer

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552292-08-7

500.48

C25H26F6N2O2

>98% (HPLC)

DMSO : ≥ 30 mg/mL; 59.94 mM

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

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(-20℃)

With Ice Pack

≥ 2 years