product name MC1568
Description: MC1568 is a novel, potent and specific inhibitor of class II HDAC, including two subclasses IIa (HDAC4/5/6/7/9) and IIb (HDAC6/10), that exhibits strong inhibition against maize class II HDAC with 50% inhibition concentration IC50 value of 22 μM. MC1568 has been found to tissue-selectively inhibits HDAC and arrest myogenesis in cultured muscle cells through three possible mechanisms, including decreasing the expression of myocyte enhancer factor 2D, stabilizing the HDAC-HDAC3-MEF2D complex and inhibiting the acetylation of differentiation-induced MEF2D.
References: J Med Chem. 2005;48(9):3344-53; J Mol Endocrinol. 2010;45(4):219-28; Diabetes. 2011;60(11):2861-71.
314.31
Formula
C17H15FN2O3
CAS No.
852475-26-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 13 mg/mL (41.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% CMC: 5 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19425535
| In Vitro |
In vitro activity: MC1568 is a selective class II (IIa) histone deacetylas (HDAC II) inhibitor with IC50 of 220 nM and 176-fold class II selectivity (against class I). In human breast cancer ZR-75.1 cell lysates, MC1568 (5 μM) shows no inhibitory activity against HDAC1 but is able to inhibit HDAC4. In MCF-7 cells, MC1568 (20 μM) increases the accumulation of acetylated H3 and H4 histones, as well as the levels of acetyl-tubulin, which indicates a inhibitory effect of MC1568 on HDAC6. In C2C12 cells, MC1568 (5 μM) arrests myogenesis by decreasing myocyte enhancer factor 2D (MEF2D) expression, stabilizing the HDAC4-HDAC3-MEF2D complex, and by inhibiting differentiation-induced MEF2D acetylation. MC1568 (5 or 10 μM) interferes with the RAR- and PPARγ-mediated differentiation-inducing signaling pathways. In F9 cells, MC1568 specifically blocks endodermal differentiation despite not affecting retinoic acid-induced maturation of promyelocytic NB4 cells. In 3T3-L1 cells, MC1568 attenuates PPARγ-induced adipogenesis. Kinase Assay: The enzyme liberats tritiated acetic acid from the substrate, which is quantified by scintillation counting. IC50 values are results of triple determinations. A 50 μL sample of maize enzyme (at 30 °C) is incubated (30 min) with 10 μL of total [3H]acetate-prelabeled chicken reticulocyte histones (2 mg/mL). Reaction is stopped by addition of 50 μL of 1 M HCl/0.4 M acetate and 800 μL of ethyl acetate. After centrifugation (1×104 g, 5 min), an aliquot of 600 μL of the upper phase is counted for radioactivity in 3 mL of liquid scintillation cocktail. MC1568 is tested at a starting concentration of 40 μM, and active substances are diluted further. NaB, VPA, TSA, SAHA, 85 TPX, HC-toxin, and tubacin are used as the reference compounds, and blank solvents are used as negative controls. Cell Assay: The 3T3-L1 cells are propagated and differentiated using a cocktail of isobutylmethylxanthine, dexamethasone, and insulin. From the second day post-confluence and throughout the differentiation period of 8 days, the 3T3-L1 cells are induced by: (1) no induction: at post-confluence and throughout the differentiation period of 8 days, the cells are incubated with DMSO or MC1568. (2) troglitazone: at post-confluence and throughout the differentiation period of 8 days, the cells are induced with 5 μM troglitazone, MC1568, or both. (3) rosiglitazone: at post-confluence and throughout the differentiation period of 8 days, the cells are incubated with 1 μM rosiglitazone and either DMSO or MC1568. (4) rosiglitazone and dexamethasone: at post-confluence, the cells received 1 μM of rosiglitazone and 390 ng/mL dexamethasone. Throughout the differentiation period of 8 days, the cells are induced with 1 μM of rosiglitazone and either DMSO or MC1568. All medium is renewed every second day. |
|---|---|
| In Vivo | In mice, MC1568 (50 mg/kg) shows an 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. In reporting PPRE-Luc mice, MC1568 (50 mg/kg) impairs PPARγ signaling mostly in the heart and adipose tissues. 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. |
| Animal model | PPRE-Luc transgenic mouse (C57BL/6) |
| Formulation & Dosage | Dissolved in water solution of 0.5% carbossimetilcellulose; 50 mg/kg; Oral gavage |
| References | J Med Chem. 2005 May 5;48(9):3344-53; J Mol Endocrinol. 2010 Oct;45(4):219-28; Diabetes. 2011 Nov;60(11):2861-71. |
