C646 |
Catalog No.GC12733
One-Click Copy Product Info
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C646은 강력하고 선택적인 p300/CBP 히스톤 아세틸전이효소 억제제(Ki 400nM)로 신경 보호, 항암 및 항상피-간섭 변환(anti-EMT) 효과 등 다양항 작용을 가지고 있다.
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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C646은 강력하고 선택적인 p300/CBP 히스톤 아세틸전이효소 억제제(Ki 400nM)로 신경 보호, 항암 및 항상피-간섭 변환(anti-EMT) 효과 등 다양항 작용을 가지고 있다.
C646(10µM; 2시간)은 LPS가 자극한 사이토카인 생산을 억제한다[5]. C646(10-50µM)는 히스톤 H3 아세틸화와 췌장암 세포의 증식을 억제한다[6]. C646(20µM; 4시간)은 인슐린이 없는 상태에서 인슐린 신호를 활성화하고 Hepa1-6 세포에서 인슐린 수용체 단백질 기질(IRS) 막 전이를 증가시킨다[7].
C646(10µl; 매일 한 번 투여; 7일)은 기계적 동종증 및 열적 과민증를 완화시키고 척수에서 COX-2 표현을 억제함과 동반되었다[8]. C646(1µg/g; i.v; 14일) 치료는 p300 및 H3K56 아세틸화를 완화시키고 내피세포(EC) 기능장애를 개선하고 NF-κB를 억제함으로써 동맥경도와 관상동맥피기능 셀라의 유동(CFR)을 개선한다[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.
| 세포 실험 [1]: | |
세포 라인 | 쥐 뼈수에서 유래된 대식시포(BMDMs) |
제조 방법 | 이 실험에서는 영동적으로 14C 표시된 Ac-H4-15의 생성을 모니터링합니다. 반응은 20 mM HEPES (pH 7.9)에서 수행되고 5 mM DTT, 80 µM EDTA, 40 µg/ml BSA, 100 µM H4-15, 5 nM p300을 포함하고 있습니다. DMSO는 2.5%로 일정하게 유지되고 억제제(C646 포함)는 25 µM에서 검사됩니다. 반응은 30°C에서 10분 동안 인슐린 후 12C-acetyl-CoA와 14C-acetyl-CoA의 1:1 혼합물을 추가하여 최종 농도 20 µM로 시작되고 30°C에서 10분 동안 진행됩니다. 그 후 14% SDS (w/v)를 추가하여 반응을 중지시킵니다. 전환률은 10% 이하로 유지됩니다. |
반응 조건 | 10µM；2 시간 동안 |
응용 분야 | C646은 경쟁적인 p300 억제제로서 Ki 값이 400nM이고 다른 아세틸전이효소에 대해 선택성을 가지고 있습니다. |
| 동물 실험 [2]: | |
동물 모형 | 수컷 Sprague-Dawley 쥐 (Chronic constriction 손상 (CCI) 모델) |
제조 방법 | C646은 요추 내막내 주입관을 통해 투여되었습니다. C646 치료를 받은 쥐는 CCI 수술 후 7일부터 14일까지 매일 C646 (10µl, 10% DMSO로 희석, 매일 한 번 투여)를 받았습니다. 매개체나 약물을 투여한 후 주입관은 5µl 0.9% 식염수로 씻겼습니다. |
제형 | 10 ul; 매일 한번; 7일 동안 |
응용 분야 | C646은 기계적 동종증상과 열적 과민증을 완화시키고 척수에서 COX-2 표현을 억제함과 동시에 이루어졌습니다. |
참고문헌: [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.[2]. 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.[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. | |
| 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 |
| Solubility | ≥ 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)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
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.)