Efficient Hit-to-Lead Searching of Kinase Inhibitor Chemical Space via Computational Fragment Merging.

ABSTRACT: In early-stage drug discovery, the hit-to-lead optimization (or "hit expansion") stage entails starting from a newly identified active compound and improving its potency or other properties. Traditionally, this process relies on synthesizing and evaluating a series of analogues to build up structure-activity relationships. Here, we describe a computational strategy focused on kinase inhibitors, intended to expedite the process of identifying analogues with improved potency. Our protocol begins from an inhibitor of the target kinase and generalizes the synthetic route used to access it. By searching for commercially available replacements for the individual building blocks used to make the parent inhibitor, we compile an enumerated library of compounds that can be accessed using the same ch

SUBMITTER: Andrianov GV 

PROVIDER: S-EPMC8865965 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature