Rolapitant hydrochloride hydrate (SCH619734 hydrochloride hydrate) 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 hydrate 不与 CYP3A4 产生互作。Rolapitant hydrochloride hydrate 在雪貂呕吐模型中显示出强效的止吐活性。
| 生物活性 | Rolapitant hydrochloride hydrate (SCH619734 hydrochloride hydrate) is a potent, selective, long-acting and orally activeneurokinin 1 (NK1) receptorantagonist with aKiof 0.66 nM. Rolapitant hydrochloride hydrate does not interact with CYP3A4. Rolapitant hydrochloride hydrate shows potent anti-emetic activity in a ferret emesis model[1][2]. |
| IC50& Target[1] | human NK1 0.66 nM (Ki) | gerbil NK1 0.13 nM (Ki) | guinea pig NK1 0.72 nM (Ki) | monkey NK1 2.5 nM (Ki) | rabbit NK1 31.7 nM (Ki) | rat NK1 78.6 nM (Ki) | mouse NK1 60.4 nM (Ki) |
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体外研究
(In Vitro) | Rolapitant hydrochloride hydrate 对人类 NK2 和 NK3 亚型的选择性超过 1000 倍，并且对人类、豚鼠、沙鼠和猴子 NK1 受体的亲和力优于大鼠、小鼠和兔[1].
Rolapitant hydrochloride hydrate (1-1000 nM) 在表达人 NK1 受体的 CHO 细胞中以浓度依赖性和竞争性方式抑制 GR-73632 (一种 NK1 受体激动剂) 诱导的钙流出[1]。
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体内研究
(In Vivo) | Rolapitant hydrochloride hydrate (0.03-1 mg/kg for PO, 0.3-1 mg/kg for IV; single dosage) 减弱蒙古沙鼠中GR-73632(HY-P1192) 诱导的足部敲击反应[1]。
Rolapitant hydrochloride hydrate (0.03-1 mg/kg; PO; single dosage; observed for 72 h) 阻断雪貂中由阿扑吗啡和cisplatin(HY-17394) 引起的急性呕吐[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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