C646 |
| Catalog No.GC12733 |
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.
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.
;)
_1-7.$$$37316672@70.jpg');)
;)
;)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
;)
;)
;)
_1124-1138.$$$35908550@30.jpg');)
_766-780.$$$37100057@30.jpg');)
_418-432.$$$36893736@30.jpg');)
_240-255.$$$35108512@29.jpg');)
_533-545.$$$36543525@28.jpg');)
_264-276.$$$36600053@22.jpg');)
_2214998.$$$@0.jpg');)
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.
| Cell experiment [1]: | |
|
Cell lines |
Mouse bone marrow-derived macrophages (BMDMs) |
|
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%. |
|
Reaction Conditions |
10µM；2 h |
|
Applications |
C646 is a competitive p300 inhibitor with a Ki of 400 nM and is selective versus other acetyltransferases. |
| Animal experiment [2]: | |
|
Animal models |
Male Sprague-Dawley rats (Chronic constriction injury (CCI) model) |
|
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. |
|
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 | |
| 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. |
||
| 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 | 0.449 mL | 2.2451 mL | 4.4901 mL |
| 10 mM | 0.2245 mL | 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 ddH2O, 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%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 25 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *