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。
| 生物活性 | Rolapitant (SCH619734) hydrochloride is a potent, selective, long-acting and orally activeneurokinin 1 (NK1) receptorantagonist with aKiof 0.66 nM. Rolapitant hydrochloride does not interact with CYP3A4. Rolapitant hydrochloride shows potent anti-emetic activity in a ferret emesis model[1][2]. |
| IC50& Target[1] | human NK1 0.66 (Ki) | gerbil NK1 0.13 (Ki) | guinea pig NK1 0.72 (Ki) | monkey NK1 2.5 (Ki) | rabbit NK1 31.7 (Ki) | rat NK1 78.6 (Ki) | mouse NK1 60.4 (Ki) |
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体外研究
(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[1].
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[1].
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体内研究
(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[1].
Rolapitant (0.03-1 mg/kg; PO; single dosage; observed for 72 h) blocks acute emesis induced by both apomorphine and cisplatin in ferrets[1].
| 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)[1] | | 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 ID90of 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)[1] | | 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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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