Strategies To Design Selective Histone Deacetylase Inhibitors.

Autor: Melesina J; Institute of Pharmacy, Martin Luther University of Halle - Wittenberg, Kurt Mothes Straße 3, 06120, Halle (Saale), Germany., Simoben CV; Institute of Pharmacy, Martin Luther University of Halle - Wittenberg, Kurt Mothes Straße 3, 06120, Halle (Saale), Germany., Praetorius L; Institute of Pharmacy, Martin Luther University of Halle - Wittenberg, Kurt Mothes Straße 3, 06120, Halle (Saale), Germany., Bülbül EF; Institute of Pharmacy, Martin Luther University of Halle - Wittenberg, Kurt Mothes Straße 3, 06120, Halle (Saale), Germany., Robaa D; Institute of Pharmacy, Martin Luther University of Halle - Wittenberg, Kurt Mothes Straße 3, 06120, Halle (Saale), Germany., Sippl W; Institute of Pharmacy, Martin Luther University of Halle - Wittenberg, Kurt Mothes Straße 3, 06120, Halle (Saale), Germany.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2021 May 06; Vol. 16 (9), pp. 1336-1359. Date of Electronic Publication: 2021 Feb 19.
DOI: 10.1002/cmdc.202000934
Abstrakt: 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 each narrating how optimization of one of six 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 the addition of groups targeting class-specific sub-pockets: the side-pocket-, lower-pocket- and foot-pocket-targeting groups. The review is rounded off with a conclusion and an outlook on the future of HDAC inhibitor design.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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