Discovery of LRRK2 inhibitors by using an ensemble of virtual screening methods. Issue 11 (1st June 2017)

• Record Type: Journal Article
• Authors: Gancia, Emanuela; De Groot, Marcel; Burton, Brenda; Clark, David E.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 11(2017)
• Page Start: 2520
• Page End: 2527
• Publication Date: 2017-06-01
• Subjects: LRRK2 -- Virtual screening -- Parkinson's disease -- Homology modelling; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.03.098
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In this paper, we present the results of a ligand- and structure-based virtual screen targeting LRRK2, a kinase that has been implicated in Parkinson's disease. For the ligand-based virtual screen, the structures of 12 competitor compounds were used as queries for a variety of 2D and 3D searches. The structure-based virtual screen relied on homology models of LRRK2, as no X-ray structure is currently available in the public domain. From the virtual screening, 662 compounds were purchased, of which 35 showed IC50 values below 10 μM in wild-type and/or mutant LRRK2 (a hit rate of 5.3%). Of these 35 hits, four were deemed to have potential for medicinal chemistry follow-up.