Cell biologist’s perspective: frontiers in the development of PROTAC-HDAC degraders

This “Minireview and Perspective” article describes histone deacetylases (HDACs), as promising specific molecular targets to treat a variety of disease states by downregulating the expression associated proteins with use new generation bioengineered compounds called protein targeting chimeras (PROTACs). We present classification HDACs, discuss their functions key epigenetic regulators gene expression, describe roles in biology aging, histone- nonhistone substrates HDACs functions, briefly introduce concept histone-modifying multiprotein complexes. Insight into biological comes from genetic knockout studies individual genes encoding deacetylases. Initially discovered newly developed HDAC inhibitors are powerful tools investigate cells organs, that have also been successfully used numerous preclinical clinical studies, drug candidates. focus on cellular mechanisms action, PROTACs, which bivalent degrader molecules recently target HDACs. then recent focused designing testing several classes selective nonselective degraders terms action. Finally, we open questions perspectives developing next HDAC-degraders.