Structural binding site comparisons reveal Crizotinib as a novel LRRK2 inhibitor.

ABSTRACT: Mutations in leucine-rich repeat kinase 2 (LRRK2) are a frequent cause of autosomal dominant Parkinson's disease (PD) and have been associated with familial and sporadic PD. Reducing the kinase activity of LRRK2 is a promising therapeutic strategy since pathogenic mutations increase the kinase activity. Several small-molecule LRRK2 inhibitors are currently under investigation for the treatment of PD. However, drug discovery and development are always accompanied by high costs and a risk of late failure. The use of already approved drugs for a new indication, which is known as drug repositioning, can reduce the cost and risk. In this study, we applied a structure-based drug repositioning approach to identify new LRRK2 inhibitors that are already approved for a different indication. In a lar

SUBMITTER: Bolz SN 

PROVIDER: S-EPMC8258795 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature