In-silico guided chemical exploration of KDM4A fragments hits.

ABSTRACT:

Background

Lysine demethylase enzymes (KDMs) are an emerging class of therapeutic targets, that catalyse the removal of methyl marks from histone lysine residues regulating chromatin structure and gene expression. KDM4A isoform plays an important role in the epigenetic dysregulation in various cancers and is linked to aggressive disease and poor clinical outcomes. Despite several efforts, the KDM4 family lacks successful specific molecular inhibitors.

Results

Herein, starting from a structure-based fragments virtual screening campaign we developed a synergic framework as a guide to rationally design efficient KDM4A inhibitors. Commercial libraries were used to create a fragments collection and perform a virtual screening campaign combining docking and pharmacophore approache

SUBMITTER: Lombino J 

PROVIDER: S-EPMC10740270 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature