Discovery of Kinase and Carbonic Anhydrase Dual Inhibitors by Machine Learning Classification and Experiments.

ABSTRACT: A multi-target small molecule modulator is advantageous for treating complicated diseases such as cancers. However, the strategy and application for discovering a multi-target modulator have been less reported. This study presents the dual inhibitors for kinase and carbonic anhydrase (CA) predicted by machine learning (ML) classifiers, and validated by biochemical and biophysical experiments. ML trained by CA I and CA II inhibitor molecular fingerprints predicted candidates from the protein-specific bioactive molecules approved or under clinical trials. For experimental tests, three sulfonamide-containing kinase inhibitors, 5932, 5946, and 6046, were chosen. The enzyme assays with CA I, CA II, CA IX, and CA XII have allowed the quantitative comparison in the molecules'

SUBMITTER: Kim MJ 

PROVIDER: S-EPMC8875555 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature