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In vivo PK/PD profile of Compound A,
a brain penetrant, orally available potent and selective LRRK2 inhibitor, in rodent and non-rodent species
Authors
Arnaud François, Pascal Grondin, Guillaume Das Dores, Aurore Sors, Anne-Pascale Luzy, Cédric Vinson, Yann Lamotte, Petra Blom, Arnaud Le Tiran, Laurence Danober, Johannes Krupp, Jan Hoflack and Nicolas Ancellin
Objectives
Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) are the most common genetic cause of Parkinson’s disease, leading to the development of LRRK2 inhibitors as potential therapeutic approach. Among them, Compound A has recently been selected as a potent, selective and brain-penetrant LRRK2 inhibitor. In order to confirm its in vivo target engagement and equipotency on wild type and G2019S LRRK2 mutants, several Pharmacokinetic/Pharmacodynamic (PK/PD) studies were performed in rodent and non-rodent species.
Prepared in collaboration with Servier
Please see the accompanying poster for the In vitro pharmacological profile of compound A