Description
Histone deacetylase 6 (HDAC6) is a class II HDAC that represses transcription by removing acetyl groups from histones. In addition, HDAC6 deacetylases tubulin, which is important in regulating microtubule stability and function. CAY10603 is a potent and selective inhibitor of HDAC6 (IC50 = 0.002 nM, as compared with 271, 252, 0.42, 6851, and 90.7 nM for HDAC1, 2, 3, 8, and 10, respectively). Also, CAY10603 prevents the growth of several pancreatic cancer cell lines (IC50 = 0.1-1 μM). The HDAC6 inhibitor is more active in inhibiting cell growth than the broad spectrum HDAC inhibitor suberoylanilide hydroxamic acid (SAHA).
Uses
Selective HDAC6 inhibitor (IC50=0.002nM). IC50 values for other HDACs are 271, 252, 0.42, 6851 and 90.7 nM for HDACs 1,2,3,8 and 10 respectively. Potent inhibitor of the proliferation of a variety of pancreatic cancer cell lines (IC50s in the 0.1-0.6μM range).
Definition
ChEBI: N-[4-[3-[[[7-(hydroxyamino)-7-oxoheptyl]amino]-oxomethyl]-5-isoxazolyl]phenyl]carbamic acid tert-butyl ester is a carbamate ester.
General Description
A cell-permeable, active site Zn2+-targeting phenylisoxazolo-hydroxamate that acts a potent and highly selective HDAC6 inhibitor (IC50 = 0.002, 0.42, 90.7, 252, 271 and 6851 nM against HDAC-6, -3, -10, -2, -1 and -8, respectively). Shown to be more potent than SAHA in inhibiting the proliferation of a panel of pancreatic cancer cell lines (IC50<1.0 μM).
IC 50
HDAC6: 0.002 nM (IC50); HDAC3: 0.42 nM (IC50); HDAC10: 90.7 nM (IC50); HDAC2: 252 nM (IC50); HDAC1: 271 nM (IC50); HDAC8: 6851 nM (IC50)
References
[1] ALAN P. KOZIKOWSKI*. Use of the Nitrile Oxide Cycloaddition (NOC) Reaction for Molecular Probe Generation: A New Class of Enzyme Selective Histone Deacetylase Inhibitors (HDACIs) Showing Picomolar Activity at HDAC6[J]. Journal of Medicinal Chemistry, 2008, 51 15: 4370-4373. DOI:
10.1021/jm8002894
