Discovery of a novel cyclin-dependent kinase 8 inhibitor with an oxindole core for anti-inflammatory treatment.

ABSTRACT: Chronic inflammation is an underlying cause in a number of diseases. Cyclin-dependent kinase 8 (CDK8) has been implicated as an inflammatory mediator, indicating its potential as an anti-inflammatory target. Herein, we performed structure-based virtual screening (SBVS) to identify novel CDK8 inhibitors. The pharmacological interactions for CDK8 were identified and incorporated into a SBVS protocol. Selected compounds were tested in enzymatic assays, and one compound was confirmed to be a CDK8 inhibitor with a 50% inhibitory concentration (IC₅₀) value of 1684.4 nM. Comparing structural analogs identified a compound, F059-1017, with greater potency (IC₅₀ 558.1 nM). When tested in cell lines, the compounds displayed low cytotoxicity. Cellular assays revealed that the ide

SUBMITTER: Lin TE 

PROVIDER: S-EPMC8776612 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature