Rolapitant hydrochloride B

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Rolapitant (SCH619734) hydrochloride 是一种长效且具有选择性和口服活性的神经激肽 1 (NK1) 受体拮抗剂，Ki 值为 0.66 nM。Rolapitant hydrochloride 不与 CYP3A4 产生互作。Rolapitant hydrochloride 在雪貂呕吐模型中显示出强效的止吐活性。

Rolapitant (SCH619734) hydrochloride is a potent, selective, long-acting and orally active neurokinin 1 (NK1) receptor antagonist with a Ki of 0.66 nM. Rolapitant hydrochloride does not interact with CYP3A4. Rolapitant hydrochloride shows potent anti-emetic activity in a ferret emesis model.

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 IVAdministration:PO or IV, single dosageResult: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.

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GPCR/G Protein

Neurokinin Receptor

Neurokinin receptor

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858102-79-1

536.94

C25H27ClF6N2O2

>98% (HPLC)

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Cl.C[C@@H](OC[C@]1(CC[C@]2(CCC(=O)N2)CN1)c1ccccc1)c1cc(cc(c1)C(F)(F)F)C(F)(F)F

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(-20℃)

With Ice Pack

≥ 2 years