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C646

现货
Catalog No.
B1577
HAT p300-CBP抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,050.00
现货
10mg
¥ 1,030.00
现货
50mg
¥ 3,990.00
现货

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Background

C646, a pyrazolone-containing small molecule, is a cell-permeable histone acetyltransferase (HAT) inhibitor that competitively and selectively inhibits the HAT activity of p300, a transcriptional co-activator involved in a variety of gene regulatory pathways and protein acetylation events, with the inhibition constant Ki value of 400 nM and the half maximal inhibition concentration IC50 value of 1.6 μM [1].

C646 binds to p300 as the Z-isomer forming hydrogen bonds between Thr1411, tYR1467, Trp1466 and Arg1410 on the side chains of p300 and oxygen atoms of C646 [1].

C646 is also capable of inhibiting a variety of p300 HAT mutants, including T1411A, Y1467F, W1466F and R1410A with IC50 values of 3.4 μM, 7 μM, 5 μM and 2.5 μM respectively [1].

Reference

References:
[1] Bowers EM, Yan G, Mukherjee C, Orry A, Wang L, Holbert MA, Crump NT, Hazzalin CA, Liszczak G, Yuan H, Larocca C, Saldanha SA, Abagyan R, Sun Y, Meyers DJ, Marmorstein R, Mahadevan LC, Alani RM, Cole PA. Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Chem Biol. 2010 May 28;17(5):471-82. doi: 10.1016/j.chembiol.2010.03.006.

文献引用

1. Li N, Yang L, et al. "BET bromodomain inhibitor JQ1 preferentially suppresses EBV-positive nasopharyngeal carcinoma cells partially through repressing c-Myc." Cell Death Dis. 2018 Jul 9;9(7):761. PMID:29988031

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt445.42
Cas No.328968-36-1
FormulaC24H19N3O6
Solubility≥11.1mg/mL in DMSO
Chemical Name4-[(4Z)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid
SDFDownload SDF
Canonical SMILESCC1=C(C=C(C(=C1)C2=CC=C(O2)C=C3C(=NN(C3=O)C4=CC=C(C=C4)C(=O)O)C)[N+](=O)[O-])C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

放射性检测

使用直接放射性实验测定假定的p300 HAT抑制剂的IC50值。反应在20 mM HEPES (pH 7.9)中进行,包含5 mM DTT, 80 μM EDTA, 40 μg/ml BSA, 100 μM H4-15, 和 5 nM p300。加入一定浓度范围的假定抑制剂,DMSO 浓度保持不变(<5%)。反应在30°C 下温育10分钟, 然后加入1:1 12C-acetyl-CoA 和 14C-acetyl-CoA 的混合物到 20 mM,开始反应。在30°C下进行10分钟后,使用14% SDS (w/v) 淬火。所有浓度按一式两份筛选。跑胶,洗涤,干燥,暴露于PhosphorImager板上,对产生的Ac-H4-15进行量化,得到IC50值。

细胞实验 [2]:

细胞系

RAW264.7鼠巨噬细胞

溶解方法

该化合物在DMSO中的溶解度> 10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应时间

1,5,10,15,20,25或30 μM,持续16小时;15或30 μM,6小时,或30 μM,20小时

应用

C646处理RAW264.7鼠巨噬细胞,减少促炎基因表达和NF-kB活性并抑制组蛋白去乙酰化酶活性。 此外,C646处理RAW264.7细胞,减少α-微管蛋白乙酰化。

动物实验 [3]:

动物模型

C57BL / 6雄性小鼠模型

剂量

每种情况下2×0.75 μl 注射体积、1.5 μg、处理超过2分钟

应用

C646抑制下颌前额叶皮层(ILPFC)中的p300,增强恐惧消光记忆的形成。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

1Bowers, E. M., Yan, G., Mukherjee, C., Orry, A., Wang, L., Holbert, M. A., Crump, N. T., Hazzalin, C. A., Liszczak, G., Yuan, H., Larocca, C., Saldanha, S. A., Abagyan, R., Sun, Y., Meyers, D. J., Marmorstein, R., Mahadevan, L. C., Alani, R. M. and Cole, P. A. (2010) Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Chem Biol. 17, 471-4822

2van den Bosch, T., Boichenko, A., Leus, N. G., Ourailidou, M. E., Wapenaar, H., Rotili, D., Mai, A., Imhof, A., Bischoff, R., Haisma, H. J. and Dekker, F. J. (2016) The histone acetyltransferase p300 inhibitor C646 reduces pro-inflammatory gene expression and inhibits histone deacetylases. Biochem Pharmacol. 102, 130-140

3Marek, R., Coelho, C. M., Sullivan, R. K., Baker-Andresen, D., Li, X., Ratnu, V., Dudley, K. J., Meyers, D., Mukherjee, C., Cole, P. A., Sah, P. and Bredy, T. W. (2011) Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300. J Neurosci. 31, 7486-7491

生物活性

描述 C646是p300的抑制剂,Ki值为400 nM。
靶点 p300/CBP          
IC50 400 nM(Ki)          

质量控制

化学结构

C646

相关生物数据

C646