MLi-2, a Potent, Selective, and Centrally Active Compound for Exploring the Therapeutic Potential and Safety of LRRK2 Kinase Inhibition

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 355; no. 3; pp. 397 - 409
• Main Authors: Fell, Matthew J, Mirescu, Christian, Basu, Kallol, Cheewatrakoolpong, Boonlert, DeMong, Duane E, Ellis, J Michael, Hyde, Lynn A, Lin, Yinghui, Markgraf, Carrie G, Mei, Hong, Miller, Michael, Poulet, Frederique M, Scott, Jack D, Smith, Michelle D, Yin, Zhizhang, Zhou, Xiaoping, Parker, Eric M, Kennedy, Matthew E, Morrow, John A
• Format: Journal Article
• Language: English
• Published: United States 01.12.2015
• Subjects: Alveolar Epithelial Cells - drug effects; Alveolar Epithelial Cells - pathology; Animals; Antiparkinson Agents - adverse effects; Antiparkinson Agents - therapeutic use; Behavior, Animal - drug effects; Binding, Competitive; Brain - metabolism; Brain Chemistry - drug effects; Cell Line; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Dose-Response Relationship, Drug; Humans; Indazoles - pharmacology; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Lung - pathology; Male; Mice; Mice, Inbred C57BL; Mutation - genetics; Parkinson Disease - drug therapy; Parkinson Disease - pathology; Parkinson Disease - psychology; Phosphorylation; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Pyrimidines - pharmacology

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of familial and sporadic Parkinson's disease (PD). That the most prevalent mutation, G2019S, leads to increased kinase activity has led to a concerted effort to identify LRRK2 kinase inhibitors as a pot...