C646
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
C646，含吡唑啉酮的小分子，是一种细胞通透性的组蛋白乙酰转移酶（HAT）抑制剂，竞争性和选择性地抑制p300的HAT活性，Ki和IC50值分别为400 nM和1.6 μM。p300是参与各种基因调控途径和蛋白乙酰化事件的转录共激活子[1]。
C646与p300结合，在C646的氧原子和p300侧链上的Thr1411、tYR1467、Trp1466和Arg1410之间形成氢键[1]。C646也能够抑制各种p300 HAT突变，包括T1411A、Y1467F、W1466F和R1410A，IC50值分别为3.4 μM、7 μM、5 μM和2.5 μM[1]。
参考文献：
[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.
- 1. Jiang W, Yuan X, et al. "Inhibition of Histone H3K27 Acetylation Orchestrates Interleukin-9-Mediated and Plays an Anti-Inflammatory Role in Cisplatin-Induced Acute Kidney Injury." Front Immunol. 2020;11:231. PMID:32194547
- 2. 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
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 445.42 |
| Cas No. | 328968-36-1 |
| Formula | C24H19N3O6 |
| Solubility | insoluble in H2O; ≥11.14 mg/mL in DMSO; ≥3.29 mg/mL in EtOH with ultrasonic |
| Chemical Name | 4-[(4Z)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid |
| SDF | Download SDF |
| Canonical SMILES | CC1=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 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 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( |
| 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]: | |
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动物模型 |
C57BL / 6雄性小鼠模型 |
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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。 |
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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 |
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| 描述 | C646是p300的抑制剂，Ki值为400 nM。 | |||||
| 靶点 | p300/CBP | |||||
| IC50 | 400 nM(Ki) | |||||
质量控制和MSDS
- 批次:
化学结构
相关生物数据
相关生物数据
