MC1568

Item no.	S1484-10
Manufacturer	Selleckchem
CASRN	852475-26-4
Amount	10 mg
Quantity options	10 mg 1 g 10 g 10 mM/1 ml 25 mg 5 mg 5 g
Category	Oncology Food Safety Drugs Neuroscience Metabolism Diabetes Cholesterol & Lipid Metabolism Regulation of Appetite Aging & Neurological Disorders Neural Epigenetics Inhibitors & Compound Libraries Small Molecules By Organ Breast Cancer
Type	Inhibitors
Specific against	other
Smiles	CN1C=C(C=C1C=CC(=O)NO)C=CC(=O)C2=CC(=CC=C2)F
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	HDAC,HDAC
Similar products	MC1568
Available
Storage Conditions	2 years -80 in solvent
Molecular Weight	314, 31
Administration	By gavage once a day
Animal Models	PPRE-Luc transgenic mouse (C57BL/6)
Cell lines	3T3-L1 cells
Concentrations	ca.10 uM, dissolved in DMSO
Dosages	50 mg/kg
Formulation	Dissolved in water solution of 0.5% carbossimetilcellulose
IC50	220 nM [1], 220 nM [1], 220 nM [1], 220 nM [1], 220 nM [1], 220 nM [1]
In vitro	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 uM) shows no inhibitory activity against HDAC1 but is able to inhibit HDAC4. [1] In MCF-7 cells, MC1568 (20 uM) 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. [2] In C2C12 cells, MC1568 (5 uM) arrests myogenesis by decreasing myocyte enhancer factor 2D (MEF2D) expression, stabilizing the HDAC4-HDAC3-MEF2D complex, and by inhibiting differentiation-induced MEF2D acetylation. [3] MC1568 (5 or 10 uM) interferes with the RAR- and PPARgamma-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 PPARgamma-induced adipogenesis. [4]
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. [3] In reporting PPRE-Luc mice, MC1568 (50 mg/kg) impairs PPARgamma signaling mostly in the heart and adipose tissues. [4] In a recent study of pancreatic explants, MC1568 enhances expression of Pax4, a key factor required for proper beta-and delta-cell differentiation and amplifies endocrine beta- and delta-cells. [5]
Incubation Time	8 days
Kinase Assay	Maize HD2, HD1-B, and HD1-A Enzyme Inhibition., The enzyme liberats tritiated acetic acid from the substrate, which is quantified by scintillation counting. IC50 values are results of triple determinations. A 50 uL sample of maize enzyme (at 30 C) is incubated (30 min) with 10 uL of total [3H]acetate-prelabeled chicken reticulocyte histones (2 mg/mL). Reaction is stopped by addition of 50 uL of 1 M HCl/0.4 M acetate and 800 uL of ethyl acetate. After centrifugation (1x104 g, 5 min), an aliquot of 600 uL of the upper phase is counted for radioactivity in 3 mL of liquid scintillation cocktail. MC1568 is tested at a starting concentration of 40 uM, 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.
Method	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 uM troglitazone, MC1568, or both. (3) rosiglitazone: at post-confluence and throughout the differentiation period of 8 days, the cells are incubated with 1 uM rosiglitazone and either DMSO or MC1568. (4) rosiglitazone and dexamethasone: at post-confluence, the cells received 1 uM of rosiglitazone and 390 ng/mL dexamethasone. Throughout the differentiation period of 8 days, the cells are induced with 1 uM of rosiglitazone and either DMSO or MC1568. All medium is renewed every second day.
Solubility (25C)	DMSO 13 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information	MC1568 is a selective HDAC inhibitor for maize HD1-A with IC50 of 100 nM in a cell-free assay. It is 34-fold more selective for HD1-A than HD1-B.
Chemical Name	(E)-3-(4-((E)-3-(3-fluorophenyl)-3-oxoprop-1-enyl)-1-methyl-1H-pyrrol-2-yl)-N-hydroxyacrylamide

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