JH-II-127

Описание

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 LRRK2^G2019S in vitro. It also inhibits Ser935 phosphorylation in vivo in mouse brain, spleen, and kidney when administered at a dose of 30 mg/kg.

Использование

JH-II-127 is a highly potent, selective, and brain penetrant LRRK2 inhibitor.