Troxler, Thomas J., Greenidge, Paulette, Zimmermann, Kaspar, Desrayaud, Sandrine, Drueckes, Peter, Schweizer, Tatjana, Stauffer, Daniela, Rovelli, Giorgio and Shimshek, Derya (2013) Discovery of novel indolinone-based, potent, selective and brain penetrant inhibitors of LRRK2. Bioorganic & Medicinal Chemistry Letters, 23 (14). pp. 4085-4090. ISSN 0960894X

Abstract

Mutations in leucine-rich repeat kinase-2 (LRRK2) are the most common genetic cause of Parkinson‘s disease (PD). The most frequent kinase-enhancing mutation is the G2019S residing in the kinase activation domain. This opens up a promising therapeutic avenue for drug discovery targeting the kinase activity of LRRK2 in PD. Several LRRK2 inhibitors have been reported to date. Here, we report a selective, brain penetrant LRRK2 inhibitor and demonstrate by a competition pulldown assay in vivo target engagement in mice.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:13
Last Modified:	04 Jul 2016 23:46
URI:	https://oak.novartis.com/id/eprint/9882