Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA.
Bioorg Med Chem Lett. 2012 Nov 1;22(21):6621-7. doi: 10.1016/j.bmcl.2012.08.104. Epub 2012 Sep 7.
A novel series of HDAC8 inhibitors without a zinc-chelating hydroxamic acid moiety is reported. Photoaffinity labeling and molecular modeling studies suggest that these ligands are likely to bind in an 'upside-down' fashion in a secondary binding site proximal to the main catalytic site. The most potent ligand in the series exhibits an IC(50) of 28 μM for HDAC8 and is found to inhibit the deacetylation of H4 but not α-tubulin in SH-SY5Y cell line.
本文报道了一系列新型的 HDAC8 抑制剂，它们不含锌螯合型羟肟酸基团。光亲和标记和分子模拟研究表明，这些配体可能以“倒置”的方式结合在靠近主要催化位点的次要结合位点上。该系列中最有效的配体对 HDAC8 的 IC50 为 28 μM，并且被发现能够抑制 SH-SY5Y 细胞系中 H4 的去乙酰化，但不能抑制α-微管蛋白。
