Chemical Information

Biological Activity of GNE-7915

GNE-7915 is a highly potent, selective, and brain-penetrable LRRK2 small molecule inhibitor with IC50 of 9 nM in cellular LRRK2 assay; > 100 fold selectivity against a panel of 187 kianses(Ki).
IC50 value: 9 nM (cellular assay) [1]
Target: LRRK2
GNE-7915 demonstrated excellent in vitro DMPK and in vivo rat PK profiles including minimal turnover in human hepatocytes and low total and unbound clearance values as predicted by rat hepatocytes, long half-lives, good oral exposure, high passive permeability, no human P-gp efflux, and good brain penetration in rats. GNE-7915 also showed concentration-dependent knockdown of pLRRK2 in the brain of BAC transgenic mice expressing human LRRK2 protein with the G2019S PD mutation. A pharmacodynamic inhibition model had a calculated in vivo unbound brain IC50 of 7 nM for GNE-7915.

References on GNE-7915

[1]. Estrada AA, et al. Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. J Med Chem. 2012 Nov 26;55(22):9416-33.