Isoindole-1,3-dione derivatives as RSK2 inhibitors: synthesis, molecular docking simulation and SAR analysis

Abstract

RSK2 (p90 ribosomal S6 kinase 2) is a serine/threonine kinase expressed in a variety of cancers. Molecular-targeted inhibition of RSK2 as a potential therapeutic strategy for human cancers has been documented. In this work, a series of isoindole-1,3-dione derivatives as novel RSK2 inhibitors were designed and synthesized from a hit discovered in our previous study. Some compounds were confirmed to be moderately potent RSK2 inhibitors with IC₅₀ values of about 0.5 μM. Structure–activity relationship analysis and binding mode studies by molecular docking were performed.