Trends in Kinase Selectivity: Insights for Target Class-Focused Library Screening
Journal of Medicinal Chemistry2010Vol. 54(1), pp. 54–66
Citations Over TimeTop 10% of 2010 papers
Shana Posy, Mark A. Hermsmeier, Wayne Vaccaro, Karl‐Heinz Ott, Gordon Todderud, Jonathan Lippy, George L. Trainor, Deborah A. Loughney, Stephen R. Johnson
Abstract
A kinome-wide selectivity screen of >20000 compounds with a rich representation of many structural classes has been completed. Analysis of the selectivity patterns for each class shows that a broad spectrum of structural scaffolds can achieve specificity for many kinase families. Kinase selectivity and potency are inversely correlated, a trend that is also found in a large set of kinase functional data. Although selective and nonselective compounds are mostly similar in their physicochemical characteristics, we identify specific features that are present more frequently in compounds that bind to many kinases. Our results support a scaffold-oriented approach for building compound collections to screen kinase targets.
Related Papers
- → Rigidification Dramatically Improves Inhibitor Selectivity for RAF Kinases(2019)21 cited
- → PKIS deep dive yields a chemical starting point for dark kinases and a cell active BRSK2 inhibitor(2020)18 cited
- → Identifying representative kinases for inhibitor evaluation via systematic analysis of compound-based target relationships(2020)7 cited
- → Structure Activity Relationship Studies around DB18, a Potent and Selective Inhibitor of CLK Kinases(2022)3 cited
- SHEDding light on the role of Pragmin pseudo-kinases in cancer.(2019)