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ICA-105665

CAS No. :

MCE 站：ICA-105665

产品活性：ICA-105665 (PF-04895162) 是一种有效的口服活性的神经元 Kv7.2/7.3 和 Kv7.3/7.5 钾通道激动剂。ICA-105665 抑制肝线粒体功能和胆盐输出蛋白 (BSEP) 转运 (IC₅₀ 为 311 μM). ICA-105665 可穿透血脑屏障并具有抗癫痫作用。

研究领域：Membrane Transporter/Ion Channel

作用靶点：Potassium Channel

In Vitro: ICA-105665 (PF-04895162) does not display potent cytotoxic properties in THLE ａnd HepG2 cell lines (IC₅₀ ~192 μM ａnd 130 μM after 72 hours, respectively) or in human hepatocytes (AC₅₀ for cell loss at 48 hours was >125 μM based on results in three assessments in two different human hepatocyte lots (LBN ａnd HU4165).
Mitochondrial respiratory reserve is compromised in human hepatocytes treated with ICA-105665 (PF-04895162) at concentrations >11 μM for 25 minutes.

In Vivo: For ICA-105665 (PF-04895162), in a 7-day rat toxicity study, dose-dependent alanine aminotransferase (ALT) elevations, potentially indicative of liver toxicity, were observed. However, no histological evidence of liver injury was identified, ａnd ALT elevations were not confirmed in a repeat 7-day study. Further, 28 day ａnd 6 month toxicity studies in rats were negative for transaminase elevations ａnd liver toxicity, ａnd toxicity studies up to 9 months duration in cynomolgus monkeys were also negative.
ICA-105665 (PF-04895162) has demonstrated broad spectrum antiseizure activity in multiple animal models including maximal electroshock, 6 Hz seizures, pentylenetetrazole, ａnd electrical kindling at doses from <1 to 5 mg/kg.

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