%0 Journal Article
%T HDAC3 inhibitors: a patent review of their broad-spectrum applications as therapeutic agents.
%A Makgoba TB
%A Kapp E
%A Egieyeh S
%A Joubert J
%J Expert Opin Ther Pat
%V 34
%N 4
%D 2024 Apr 25
%M 38873766
%F 6.714
%R 10.1080/13543776.2024.2363890
%X <B>UNASSIGNED: </B>Histone deacetylases (HDACs) are a class of zinc-dependent enzymes. They maintain acetylation homeostasis, with numerous biological functions and are associated with many diseases. HDAC3 strictly requires multi-subunit complex formation for activity. It is associated with the progression of numerous non-communicable diseases. Its widespread involvement in diseases makes it an epigenetic drug target. Preexisting HDAC3 inhibitors have many uses, highlighting the need for continued research in the discovery of HDAC3-selective inhibitors.<BR><B>UNASSIGNED: </B>This review provides an overview of 24 patents published from 2010 to 2023, focusing on compounds that inhibit the HDAC3 isoenzyme.<BR><B>UNASSIGNED: </B>HDAC3-selective inhibitors - pivotal for pharmacological applications, as single or combination therapies - are gaining traction as a strategy to move away from complications laden pan-HDAC inhibitors. Moreover, there is an unmet need for HDAC3 inhibitors with alternative zinc-binding groups (ZBGs) because some preexisting ZBGs have limitations related to toxicity and side effects. Difficulties in achieving HDAC3 selectivity may be due to isoform selectivity. However, advancements in computer-aided drug design and experimental data of HDAC3 3D co-crystallized models could lead to the discovery of novel HDAC3-selective inhibitors, which bear alternative ZBGs with balanced selectivity for HDAC3 and potency.