Chemical Biology of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors.
There is an urgent need for the development of Parkinson's disease (PD) treatments that can slow disease progression. The leucine-rich repeat kinase 2 (LRRK2) protein has been genetically and functionally linked to PD, and modulation of LRRK2 enzymatic activity has been proposed as a novel therapeutic strategy. In this review, we describe the bioactivity of selected small molecules that have been used to inhibit LRRK2 kinase activity in vitro or in vivo. These compounds are important tools for understanding the cellular biology of LRRK2 and for evaluating the potential of LRRK2 inhibitors as disease-modifying PD therapies.
Department of Discovery Chemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
Anthony A
AA
Estrada
Department of Discovery Chemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
Zachary K
ZK
Sweeney
D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics; D010539:Permeability; D011485:Protein Binding; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics
D000978:Antiparkinson Agents; D006160:Guanosine Triphosphate; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases