Differentiating Inhibitors of Closely Related Protein Kinases with Single- or Multi-Target Activity via Explainable Machine Learning and Feature Analysis.

ABSTRACT: Protein kinases are major drug targets. Most kinase inhibitors are directed against the adenosine triphosphate (ATP) cofactor binding site, which is largely conserved across the human kinome. Hence, such kinase inhibitors are often thought to be promiscuous. However, experimental evidence and activity data for publicly available kinase inhibitors indicate that this is not generally the case. We have investigated whether inhibitors of closely related human kinases with single- or multi-kinase activity can be differentiated on the basis of chemical structure. Therefore, a test system consisting of two distinct kinase triplets has been devised for which inhibitors with reported triple-kinase activities and corresponding single-kinase activities were assembled. Machine learning models derived

SUBMITTER: Feldmann C 

PROVIDER: S-EPMC9032434 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature