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JH-II-127 C화학적 특성, 용도, 생산
개요
JH-II-127 is an orally bioavailable inhibitor of wild-type (WT) and mutant forms of leucine-rich repeat kinase 2 (LRRK2). It inhibits WT LRRK2, as well as LRRK2 containing the G2019S and A2016T substitution mutations (IC50s = 6.6, 2.2, and 47.7 nM, respectively), which are present in certain patients with Parkinson’s disease, but not LRRK2 containing both mutations (IC50 = 3,080 nM). JH-II-127 (0.1-0.3 μM) inhibits phosphorylation of the serines at positions 910 and 935 of WT LRRK2 and LRRK2G2019Sin vitro. It also inhibits Ser935 phosphorylation in vivo in mouse brain, spleen, and kidney when administered at a dose of 30 mg/kg.
용도
JH-II-127 is a highly potent, selective, and brain penetrant LRRK2 inhibitor.