Pioneering first-in-class HDAC-ROCK inhibitors as potential multitarget anticancer agents.

ABSTRACT:

Aim

With the aim of simultaneously modulating the epigenetic system and the protein kinase pathway, we selected the enzyme histone deacetylase (HDAC) and the Rho-associated protein kinases (ROCK) as desired targets to develop potential multitarget anticancer agents with additional antimetastatic properties. We report here the rational design, synthesis, and biological evaluation of the first-in-class HDAC/ROCK multitarget inhibitors in pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer (TNBC).

Materials and methods

A molecular docking study performed with the Gold software was used to develop HDAC/ROCK multitarget inhibitors. IC₅₀ values were determined by enzyme assays. The cytotoxicity, anti-migratory and anti-invasive properties of

SUBMITTER: Beljkas M 

PROVIDER: S-EPMC11834526 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature