MC1568 is a potent and selective inhibitor of class
IIa histone deacetylases (HDACs), with IC50 of 100 nM for maize
HD1-A. It is 34-fold more selective for HD1-A than HD1-B, 176-fold more
selective for class I HDACs. It exhibits tissue-selective inhibition between
members of class II deacetylases in vivo; inhibits HDAC4 and HDAC5 in skeletal
muscle and the heart without affecting HDAC3 activity. It arrests myogenesis
through the stabilization of myocyte enhancer factor 2D (MEF2D)-HDAC3/4
complex.In a recent study of
pancreatic explants, MC1568 enhances expression of Pax4, a key factor required
for proper β-and δ-cell differentiation and amplifies endocrine β- and δ-cells.
How to Use:
In vitro:? MC1568 was used at 5-10μM final concentration
in vitro and cellular assays.
In vivo: MC1568 could be orally
dosed to mice at 50 mg/kg once per day (formulation: 0.5% CMC, 5 mg/mL). It hasan
apparent tissue-selective HDAC inhibition. In skeletal muscle and heart, MC1568
inhibits the activity of HDAC4 and HDAC5 without affecting HDAC3 activity,
thereby leaving MEF2-HDAC complexes in a repressed state.
Reference:?
1. ? ?Mai
A, et al. Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis
and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides.
(2005) J Med Chem. 48(9):3344-53.
2.?????
Mai
A, et al. Identification of two new synthetic histone deacetylase inhibitors
that modulate globin gene expression in erythroid cells from healthy donors and
patients with thalassemia. (2007) Mol Pharmacol.72(5):1111-23.
3.?????
Duong
V, et al. Specific activity of class II histone deacetylases in human breast
cancer cells.(2008) Mol Cancer Res.6(12):1908-19.
4.?????
Nebbioso
A, et al. Selective class II HDAC inhibitors impair myogenesis by modulating
the stability and activity of HDAC-MEF2 complexes. (2009) EMBO Rep.
10(7):776-82.
5. ? ?Lenoir O, et al. Specific control of pancreatic
endocrine β- and δ-cell mass by class IIa histone deacetylases HDAC4, HDAC5,
and HDAC9. (2011) Diabetes. 60(11):2861-71.
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