IC50: 0.9 nM (LRRK2 Kinase)[1]
LRRK2-IN-7 is a potent, selective, and CNS-penetrant LRRK2 kinase inhibitor with an IC50 of 0.9 nM. LRRK2-IN-7 shows >1000-fold selectivity over other kinases, ion channels, and CYP enzymes[1].
LRRK2-IN-7 (compound 25) 既是小鼠乳腺癌抗性蛋白 (BCRP) 底物（小鼠/人 BCRP）也是一种有效的人 BCRP 抑制剂（BCRP IC50 = 0.12 μM）[1] .
在一项为期 7 天的大鼠剂量限制毒性研究中，LRRK2-IN-7 (compound 25) 的耐受性高达 100 mg/kg，每天一次（AUCtot = 330 μM.h）[1]。
在大鼠急性（2 小时）PK/PD 研究中，LRRK2-IN-7 (compound 25) 显示大鼠脑纹状体中 LRRK2 pS935 剂量依赖性降低，EC50 = 0.18 nM[1]。
[1]. David A Candito, et al. Discovery and Optimization of Potent, Selective, and Brain-Penetrant 1-Heteroaryl-1 H-Indazole LRRK2 Kinase Inhibitors for the Treatment of Parkinson's Disease. J Med Chem. 2022 Dec 22;65(24):16801-16817.