1501-38-8Relevant articles and documents
Small Molecule Antagonists of the Interaction between the Histone Deacetylase 6 Zinc-Finger Domain and Ubiquitin
Harding, Rachel J.,Ferreira De Freitas, Renato,Collins, Patrick,Franzoni, Ivan,Ravichandran, Mani,Ouyang, Hui,Juarez-Ornelas, Kevin A.,Lautens, Mark,Schapira, Matthieu,Von Delft, Frank,Santhakumar, Vjayaratnam,Arrowsmith, Cheryl H.
, p. 9090 - 9096 (2017)
Inhibitors of HDAC6 have attractive potential in numerous cancers. HDAC6 inhibitors to date target the catalytic domains, but targeting the unique zinc-finger ubiquitin-binding domain (Zf-UBD) of HDAC6 may be an attractive alternative strategy. We developed X-ray crystallography and biophysical assays to identify and characterize small molecules capable of binding to the Zf-UBD and competing with ubiquitin binding. Our results revealed two adjacent ligand-able pockets of HDAC6 Zf-UBD and the first functional ligands for this domain.