Abstract
Hydroxamic acids were designed, synthesized, and evaluated for their ability to selectively inhibit human histone deacetylase 6 (HDAC6). Several inhibitors, including compound 14 (BRD9757), exhibited excellent potency and selectivity despite the absence of a surface-binding motif. The binding of these highly efficient ligands for HDAC6 is rationalized via structure-activity relationships. These results demonstrate that high selectivity and potent inhibition of HDAC6 can be achieved through careful choice of linker element only.
MeSH terms
-
HeLa Cells
-
Histone Deacetylase 6
-
Histone Deacetylase Inhibitors / chemical synthesis
-
Histone Deacetylase Inhibitors / chemistry*
-
Histone Deacetylase Inhibitors / pharmacology
-
Histone Deacetylases / chemistry*
-
Histone Deacetylases / metabolism
-
Humans
-
Hydroxamic Acids / chemical synthesis
-
Hydroxamic Acids / chemistry*
-
Hydroxamic Acids / pharmacology
-
Isoenzymes / antagonists & inhibitors
-
Isoenzymes / metabolism
-
Molecular Mimicry
-
Protein Interaction Domains and Motifs
-
Structure-Activity Relationship
Substances
-
Histone Deacetylase Inhibitors
-
Hydroxamic Acids
-
Isoenzymes
-
HDAC6 protein, human
-
Histone Deacetylase 6
-
Histone Deacetylases