ICA-105665 (PF-04895162) is a highly potent and orally bioavailable 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 (IC50 of 311 μM). ICA-105665 can penetrate the blood-brain barrier and has antiseizure effects. References: [1]. Aleo MD, et al. Phase I study of PF‐4895162, 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. [3]. Kasteleijn-Nolst Trenité DG, et al. Kv7 potassium channel activation with ICA-105665 reduces photoparoxysmal EEG responses in patients with epilepsy. Epilepsia. 2013 Aug;54(8):1437-43. [4]. Bialer M, et al. Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI). Epilepsy Res. 2013 Jan;103(1):2-30.

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