C646
目录号 : GC12733
C646是一种有效的选择性p300/CBP组蛋白乙酰转移酶抑制剂(Ki 400 nM),已被证明具有多效性,包括神经保护、抗癌和抗上皮间质转化(anti-EMT)作用。
Cas No.:328968-36-1
Sample solution is provided at 25 µL, 10mM.
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C646, a potent and selective p300/CBP histone acetyltransferase inhibitor (Ki 400 nM), has been shown to have pleiotropic activity, including neuroprotective, anti-cancer and anti-epithelial-mesenchymal transition (anti-EMT) effects[1-4].
C646(10µM; 2 h) suppresses LPS-stimulated cytokines production[5]. C646(10-50 µM) inhibits histone H3 acetylation and proliferation of pancreatic cancer cells[6]. C646(20 µM; 4 h) activates insulin signaling and increases insulin receptor protein substrates(IRS) membrane translocation in the absence of insulin in Hepa1-6 cells[7].
C646(10 ul; one dose per day; 7days) attenuated mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression in the spinal cord[8]. C646(1 µg/gm; i.v;14days) treatment attenuated p300 and H3K56 acetylation and improved arterial stiffness and Coronary flow reserve (CFR) via improvement of endothelial cell (EC) dysfunction and suppression of NF-κB[9].
References:
[1]. Oike T, Komachi M, et,al. C646, a selective small molecule inhibitor of histone acetyltransferase p300, radiosensitizes lung cancer cells by enhancing mitotic catastrophe. Radiother Oncol. 2014 May;111(2):222-7. doi: 10.1016/j.radonc.2014.03.015. Epub 2014 Apr 17. PMID: 24746574.
[2]. Yang Y, Liu K, et,al. Histone acetyltransferase inhibitor C646 reverses epithelial to mesenchymal transition of human peritoneal mesothelial cells via blocking TGF-β1/Smad3 signaling pathway in vitro. Int J Clin Exp Pathol. 2015 Mar 1;8(3):2746-54. PMID: 26045780; PMCID: PMC4440089.
[3]. Zhu XY, Huang CS, et,al. p300 exerts an epigenetic role in chronic neuropathic pain through its acetyltransferase activity in rats following chronic constriction injury (CCI). Mol Pain. 2012 Nov 23;8:84. doi: 10.1186/1744-8069-8-84. PMID: 23176208; PMCID: PMC3558366.
[4]. Bowers EM, Yan G, et,al. 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. PMID: 20534345; PMCID: PMC2884008.
[5]. Fang F, Li G, et,al. C646 modulates inflammatory response and antibacterial activity of macrophage. Int Immunopharmacol. 2019 Sep;74:105736. doi: 10.1016/j.intimp.2019.105736. Epub 2019 Jul 11. PMID: 31302452.
[6]. Ono H, Kato T, et,al. C646 inhibits G2/M cell cycle-related proteins and potentiates anti-tumor effects in pancreatic cancer. Sci Rep. 2021 May 12;11(1):10078. doi: 10.1038/s41598-021-89530-8. PMID: 33980911; PMCID: PMC8115044.
[7]. Peng J, Ramatchandirin B, et,al. The P300 acetyltransferase inhibitor C646 promotes membrane translocation of insulin receptor protein substrate and interaction with the insulin receptor. J Biol Chem. 2022 Mar;298(3):101621. doi: 10.1016/j.jbc.2022.101621. Epub 2022 Jan 21. PMID: 35074429; PMCID: PMC8850660.
[8]. Zhu XY, Huang CS, et,al. p300 exerts an epigenetic role in chronic neuropathic pain through its acetyltransferase activity in rats following chronic constriction injury (CCI). Mol Pain. 2012 Nov 23;8:84. doi: 10.1186/1744-8069-8-84. PMID: 23176208; PMCID: PMC3558366.
[9]. Su H, Zeng H, et,al. Histone Acetyltransferase p300 Inhibitor Improves Coronary Flow Reserve in SIRT3 (Sirtuin 3) Knockout Mice. J Am Heart Assoc. 2020 Sep 15;9(18):e017176. doi: 10.1161/JAHA.120.017176. Epub 2020 Aug 31. PMID: 32865093; PMCID: PMC7727016.
C646是一种有效的选择性p300/CBP组蛋白乙酰转移酶抑制剂(Ki 400 nM),已被证明具有多效性,包括神经保护、抗癌和抗上皮间质转化(anti-EMT)作用[1-4]。
C646(10µM;2 h)抑制LPS刺激的细胞因子产生[5]。C646(10-50µM)抑制组蛋白H3乙酰化和胰腺癌细胞增殖[6]。在缺乏胰岛素的Hepa1-6细胞, C646(20µM;4 h)激活胰岛素信号并增加胰岛素受体蛋白底物(IRS)膜易位 [7]。
C646 (10 ul; one dose per day; 7days)减轻了机械性异常痛和热痛觉过敏,并伴有脊髓中COX-2表达的抑制[8]。C646(1 µg/gm; i.v;14days)治疗通过改善内皮细胞(EC)功能障碍和抑制NF-κB,减轻p300和H3K56乙酰化,改善动脉僵硬和冠状动脉血流储备(CFR)[9]。
| Cell experiment [1]: | |
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Cell lines |
Mouse bone marrow-derived macrophages (BMDMs) |
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Preparation Method |
In this assay, production of 14C-labeled Ac-H4-15 is monitored electrophoretically. Reactions were performed in 20 mM HEPES (pH 7.9), and contained 5 mM DTT, 80 µM EDTA, 40 µg/ml BSA, 100 µM H4-15, and 5 nM p300. DMSO was kept constant at 2.5%, and inhibitors (including C646) were screened at 25 µM. Reactions were incubated at 30 C for 10 min, initiated with addition of a 1:1 mixture of 12C-acetyl-CoA and 14C-acetyl-CoA to a final concentration of 20 µM, and allowed to run for 10 min at 30 C. Reactions are then quenched with addition of 14% SDS (w/v). Turnover was kept below 10%. |
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Reaction Conditions |
10µM；2 h |
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Applications |
C646 is a competitive p300 inhibitor with a Ki of 400 nM and is selective versus other acetyltransferases. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague-Dawley rats (Chronic constriction injury (CCI) model) |
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Preparation Method |
C646 were administrated through the lumbar intrathecal catheter. C646-treated rats received C646 (10 ul, diluted with 10%DMSO, one dose per day) from days 7 to 14 after CCI surgery. After the vectors or drugs were administered, the catheter was flushed with 5ul 0.9% saline. |
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Dosage form |
10 ul; one dose per day; 7days |
|
Applications |
C646 attenuated mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression in the spinal cord. |
|
References: [1]. Bowers EM, Yan G, et,al. 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. PMID: 20534345; PMCID: PMC2884008. | |
| Cas No. | 328968-36-1 | SDF | |
| 化学名 | 4-[(4Z)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid | ||
| 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 | ||
| 分子式 | C24H19N3O6 | 分子量 | 445.42 |
| 溶解度 | ≥ 11.1mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2451 mL | 11.2254 mL | 22.4507 mL |
| 5 mM | 0.449 mL | 2.2451 mL | 4.4901 mL |
| 10 mM | 0.2245 mL | 1.1225 mL | 2.2451 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet