The Discovery of Small ERK5 Inhibitors via Structure-Based Virtual Screening, Biological Evaluation and MD Simulations.

ABSTRACT: ERK5, a member of the MAP kinase family, has been implicated in several cancer types due to its role in regulating cell proliferation, survival, and migration. In this study, structure-based virtual screening was employed, followed by cell assays, and molecular dynamics simulations to identify novel ERK5 inhibitors. A commercially available library of 1.6 million compounds was subjected to a three-stage docking process (HTVS, SP, and XP), using the docking module in Schrodinger Maestro, yielding 40 candidates with superior docking scores compared to the co-crystallized ligand. These compounds were then tested for antiproliferative activity using an MTT assay in A549 and H292 lung cancer cell lines. Among the hits, STK038175, STK300222, and GR04 showed significant activity with IC₅₀

SUBMITTER: Atatreh N 

PROVIDER: S-EPMC12610425 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature