(2E)-3-{4-[(1E)-3-(3-fluorophenyl)-3-oxoprop-1-en-1-yl]-1-methyl-1H-pyrrol-2-yl}-N-hydroxyprop-2-enamide

• ChemBase编号: 72706
• 分子式: C17H15FN2O3
• 平均质量: 314.3110032
• 单一同位素质量: 314.10667057
• SMILES: c1cc(cc(c1)C(=O)/C=C/c1cn(c(c1)/C=C/C(=O)NO)C)F
• Canonical SMILES: ONC(=O)/C=C/c1cc(cn1C)/C=C/C(=O)c1cccc(c1)F
• InChI: InChI=1S/C17H15FN2O3/c1-20-11-12(9-15(20)6-8-17(22)19-23)5-7-16(21)13-3-2-4-14(18)10-13/h2-11,23H,1H3,(H,19,22)/b7-5+,8-6+
• InChIKey: QRDAPCMJAOQZSU-KQQUZDAGSA-N

名称和登记号

名称

• IUPAC标准名: (2E)-3-{4-[(1E)-3-(3-fluorophenyl)-3-oxoprop-1-en-1-yl]-1-methyl-1H-pyrrol-2-yl}-N-hydroxyprop-2-enamide
• IUPAC传统名: (2E)-3-{4-[(1E)-3-(3-fluorophenyl)-3-oxoprop-1-en-1-yl]-1-methylpyrrol-2-yl}-N-hydroxyprop-2-enamide
• 别名: 3-[4-(3-(3-Fluorophenyl)-3-oxo-1-propen-1-yl)-1-methyl-1H-pyrrol-2-yl]-N-hydroxy-2-propenamide; MC 1568; MC1568

登记号

• CAS号: 852475-26-4
• PubChem SID: 162037627
• PubChem CID: 11381449

理论计算性质

• Acid pKa: 9.522503
• 质子受体: 3
• 质子供体: 2
• LogD (pH = 5.5): 2.6092637
• LogD (pH = 7.4): 2.60606
• Log P: 2.6093047
• 摩尔折射率: 87.2151 cm^3
• 极化性: 31.666971 Å^3
• 极化表面积: 71.33 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: true

分子性质

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: HDAC

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1484

Research Area

• Description: Cancer

Biological Activity

• Description: MC1568 is a selective HDAC inhibitor with IC50 of 220 nM.
• Targets: HDAC
• IC50: 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 μM) shows no inhibitory activity against HDAC1 but is able to inhibit HDAC4. ^[1]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. ^[2]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. ^[3]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. ^[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 PPARγ 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 β-and δ-cell differentiation and amplifies endocrine β- and δ-cells. ^[5]

Protocol

• Protocol: Kinase Assay ^[1]
• 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 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 (1×10^4 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.
• Protocol: Cell Assay ^[4]
• Cell Lines: 3T3-L1 cells
• Concentrations: ~10 μM, dissolved in DMSO
• Incubation Time: 8 days
• Methods: 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.
• Protocol: Animal Study ^[4]
• Animal Models: PPRE-Luc transgenic mouse (C57BL/6)
• Formulation: Dissolved in water solution of 0.5% carbossimetilcellulose
• Doses: 50 mg/kg
• Administration: By gavage once a day

References

• References: [1] Mai A, et al. J Med Chem, 2005, 48(9), 3344-3353.
• References: [2] Duong V, et al. Mol Cancer Res, 2008, 6(12), 1908-1919.
• References: [3] Nebbioso A, et al. EMBO Rep, 2009, 10(7), 776-782.
• References: [4] Nebbioso A, et al. J Mol Endocrinol, 2010, 45(4), 219-228.
• References: [5] Lenoir O, et al. Diabetes, 2011, 60(11), 2861-2871.

Toronto Research Chemicals - M199250

A selective class II (IIa) histone deacetylase (HDAC II) inhibitor. It exhibits tissue-selective inhibition between members of class II acetylases in vivo, particularly in skeletal muscle and the heart. It arrests myogenesis through the stabilization of m

参考文献

• Mai A, et al. J Med Chem, 2005, 48(9), 3344-3353.
• Duong V, et al. Mol Cancer Res, 2008, 6(12), 1908-1919.
• Nebbioso A, et al. EMBO Rep, 2009, 10(7), 776-782.
• Nebbioso A, et al. J Mol Endocrinol, 2010, 45(4), 219-228.
• Lenoir O, et al. Diabetes, 2011, 60(11), 2861-2871.
• Mai, A. et al.: Mol.Pharmacol., 72, 1111 (2007)
• Mai, A. et al.: J.Med.Chem., 48, 3344 (2007)
• Nebbioso, A. et al.: Eur. Mol. Biol. Org. Rep., 10, 776 (2007)