Strategies to Design Selective Histone Deacetylase Inhibitors.

Strategies to Design Selective Histone Deacetylase Inhibitors. ChemMedChem. 2021 Jan 11;: Authors: Sippl W, Melesina J, Simoben CV, Bülbül EF, Praetorius L, Robaa D Abstract This review classifies drug design strategies successfully implemented in the development of histone deacetylase (HDAC) inhibitors, which have many applications including cancer treatment. Our focus is on especially demanded selective HDAC inhibitors and their structure-activity relationships in relation to corresponding protein structures. The main part of the paper is divided into six subsections narrating how optimization of the six corresponding structural features can influence inhibitor selectivity. It starts with the impact of the zinc binding group on selectivity, continues with the optimization of the linker placed in the substrate binding tunnel as well as the adjustment of the cap group interacting with the surface of the protein, and ends with addition of groups targeting class-specific sub-pockets - the side pocket targeting group, the lower pocket targeting group and the foot pocket targeting group. The review is enhanced with a conclusion and an outlook to the future of HDAC inhibitor design. PMID: 33428327 [PubMed - as supplied by publisher]
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research