Upregulation of LRRK2 expression has been identified as a disease driver in a subset of Parkinson's disease patients, making inhibition of this kinase an attractive target in the search for treatment options.
In this webinar, we review a successful small molecule drug discovery project conducted by a team of scientists from Genentech and Charles River that spanned hit identification and lead optimization of a highly potent LRRK2 inhibitor. Approaches to compound-related challenges, including the requirement for selectivity over other structurally-related kinases and ensuring blood-brain barrier permeability will be discussed.
- Charles Baker-Glenn, DPhil, Team Leader, Charles River
- Discovery of Highly Potent, Selective, and Brain-Penetrant Aminopyrazole Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors. J Med Chem. 2014 Feb 13, 57 (3): 921-936. Abstract.
- Discovery of a Highly Selective, Brain-Penetrant Aminopyrazole LRRK2 Inhibitor. ACS Med. Chem. Lett. 2013, 4, 85-90. Abstract.
- Brothers in Arms: BioPharma and CROs Collaborating in Early Drug Discovery