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。

ICA-105665 (PF-04895162) is a potent and orally active neuronal Kv7.2/7.3 and Kv7.3/7.5 potassium channels opener. ICA-105665 inhibits liver mitochondrial function and bile salt export protein (BSEP) transport (IC 50 of 311 μM). ICA-105665 can penetrate the blood-brain barrier and has antiseizure effects.

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Kv7.2/7.3 and Kv7.3/7.5 potassium channels

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. has not independently confirmed the accuracy of these methods. They are for reference only.

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. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Aleo MD, et al. Phase I study of PF‐04895162, a Kv7 channel opener, reveals unexpected hepatotoxicity in healthy subjects, but not rats or monkeys: clinical evidence of disrupted bile acid homeostasis. Pharmacol Res Perspect. 2019 Feb;7(1):e00467.
[2]. Generaux G, et al. Quantitative systems toxicology (QST) reproduces species differences in PF-04895162 liver safety due to combined mitochondrial and bile acid toxicity. Pharmacol Res Perspect. 2019 Oct 9;7(6):e00523.

In Vitro: DMSO : 250 mg/mL (703.55 mM; Need ultrasonic)配制储备液