Identification of a Potent CDK8 Inhibitor Using Structure-Based Virtual Screening.

ABSTRACT: Pulmonary fibrosis is excessive scarring of the lung tissues. Transforming growth factor-beta (TGF-β) has been implicated in pulmonary fibrosis due to its ability to induce the epithelial-to-mesenchymal transition (EMT) and promote epithelial cell migration. Cyclin-dependent kinase 8 (CDK8) can mediate the TGF-β signaling pathways and could function as an alternative therapeutic target for treating pulmonary fibrosis. Here, we performed a structure-based virtual screening campaign to identify CDK8 inhibitors from a library of 1.6 million compounds. The screening process ended with the identification of a novel CDK8 inhibitor, P162-0948 (IC₅₀: 50.4 nM). An interaction analysis highlighted important CDK8-ligand interactions that support its binding and inhibitory activity. Testing

SUBMITTER: Lin TE 

PROVIDER: S-EPMC11733953 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature