Quantitative Structure-Activity Relationship Modeling of Kinase Selectivity Profiles.

ABSTRACT: The discovery of selective inhibitors of biological target proteins is the primary goal of many drug discovery campaigns. However, this goal has proven elusive, especially for inhibitors targeting the well-conserved orthosteric adenosine triphosphate (ATP) binding pocket of kinase enzymes. The human kinome is large and it is rather difficult to profile early lead compounds against around 500 targets to gain an upfront knowledge on selectivity. Further, selectivity can change drastically during derivatization of an initial lead compound. Here, we have introduced a computational model to support the profiling of compounds early in the drug discovery pipeline. On the basis of the extensive profiled activity of 70 kinase inhibitors against 379 kinases, including 81 tyrosine kinases, we develop

SUBMITTER: Kothiwale S 

PROVIDER: S-EPMC6151389 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature