Analyzing Kinase Similarity in Small Molecule and Protein Structural Space to Explore the Limits of Multi-Target Screening.

ABSTRACT: While selective inhibition is one of the key assets for a small molecule drug, many diseases can only be tackled by simultaneous inhibition of several proteins. An example where achieving selectivity is especially challenging are ligands targeting human kinases. This difficulty arises from the high structural conservation of the kinase ATP binding sites, the area targeted by most inhibitors. We investigated the possibility to identify novel small molecule ligands with pre-defined binding profiles for a series of kinase targets and anti-targets by in silico docking. The candidate ligands originating from these calculations were assayed to determine their experimental binding profiles. Compared to previous studies, the acquired hit rates were low in this specific setup, which aimed at not on

SUBMITTER: Schmidt D 

PROVIDER: S-EPMC7865522 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature