C646 |
カタログ番号GC12733
One-Click Copy Product Info
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C646は、強力かつ選択的なp300/CBPヒストンアセチルトランスフェラーゼ阻害剤(Ki 400 nM)であり、神経保護作用、抗がん作用、抗上皮間葉転換作用(anti-EMT)を有することが示されている
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 328968-36-1
Sample solution is provided at 25 µL, 10mM.
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C646は、強力かつ選択的なp300/CBPヒストンアセチルトランスフェラーゼ阻害剤(Ki 400 nM)であり、神経保護作用、抗がん作用、抗上皮間葉転換作用(anti-EMT)を有することが示されている。
C646(10µM; 2時間)はLPS誘発によるサイトカイン産生を抑制する。C646(10-50 µM)はヒストンH3のアセチル化を阻害し、膵臓がん細胞の増殖を抑制する。C646(20 µM; 4 h)はHepa1-6細胞において、インスリンシングルを活性化し、インスリン非存在下でインスリン受容体タンパク質基質(IRS)の膜移行を増加させる。
C646(10 ul; 1日1回投与; 7日間)は脊髄におけるCOX-2発見の抑制を伴って、機械的アロディニアと温熱性痛覚過敏を減弱させた。C646(1 µg/gm; i.v;14日間)投与はp300およびH3K56アセチル化を抑制し、内皮細胞(EC)機能不全の改善およびNF-κBの抑制を介して動脈硬化および冠血流予備能(CFR)を改善した。
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.
| 細胞実験[1]: | |
細胞株 | マウス骨髄由来マクロファージ（BMDMs） |
準備方法 | このアッセイにおいて、14C標識Ac-H4-15の産生は電気泳動でモニターされる。反応は20 mM HEPES (pH 7.9)で行い、5 mM DTT、80 µM EDTA、40 µg/ml BSA、100 µM H4-15、5 nM p300を加えた。DMSOは2.5%で一定に保ち、阻害剤(C646を含む)は25µMでスクリーニングした。反応は30℃で10分間インキュベートし、12C-acetyl-CoAと14C-acetyl-CoAの1:1混合物を最終濃度20 µMになるように加え、30℃で10分間反応させた。ターンオーバーは10％以下に保たれた。 |
反応条件 | 10µM；2時間 |
アプリケーション | C646は競合的p300阻害剤（Ki値は400nM）であり、ほかのセリンアセチルトランスフェラーゼに対して選択的である。 |
| 動物実験 [2]: | |
動物モデル | 雄性Sprague-Dawleyラット（絞扼性神経損傷（CCI）モデル） |
準備方法 | C646は腰椎カテーテルから投与した。C646投与ラットはCCI手術後7-14日目にC646(10 ul, 10％DMSOで希釈, 1日1回)を投与された。ベクターまたは薬剤の投与後、カテーテルを5ul 0.9%生理食塩水で洗浄した。 |
投与形態 | 10 ul; 1日1回; 7日間 |
アプリケーション | C646は脊髄におけるCOX-2発見の抑制を伴って、機械的アロディニアと温熱性痛覚過敏を減弱させた |
References: | |
| Cas No. | 328968-36-1 | SDF | |
| Chemical Name | 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 | ||
| Formula | C24H19N3O6 | M.Wt | 445.42 |
| 溶解度 | ≥ 11.1mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2451 mL | 11.2254 mL | 22.4507 mL |
| 5 mM | 449 μL | 2.2451 mL | 4.4901 mL |
| 10 mM | 224.5 μL | 1.1225 mL | 2.2451 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 25 reference(s) in Google Scholar.)