A selective LRRK2 inhibitor
Leucine-rich repeat kinase 2 (LRRK2) is an enzyme that interacts with parkin, a ligase that is part of the ubiquitin-proteasome system that mediates the targeting of proteins for degradation. Loss of function of the parkin protein leads to dopaminergic cell death. The development of Parkinson's disease has been strongly associated with mutations in the LRRK2 gene that lead to increased kinase activity. GNE-7915 is a selective, brain-penetrable LRRK2 inhibitor (Kis = 2 and 18.7 nM in biochemical and cell-based assays, respectively).1 It inhibits LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation with an IC50 value of 20 nM in vivo.1
1.Estrada, A.A., Chan, B.K., Baker-Glenn, C., et al.Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitorsJ. Med. Chem.57(3)921-936(2014)
动态评分
0.0