GLPBio

C646

Catalog No.: GC12733Purity:>98.00%
COASDSData Sheet
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.

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C646
Cas No.: 328968-36-1
10mM (in 1mL DMSO)In Stock
$76.00
1
5mgIn Stock
$43.00
1
10mgIn Stock
$69.00
1
20mgIn Stock
$112.00
1
50mgIn Stock
$217.00
1
100mgIn Stock
$350.00
1
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Description

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.

Protocol

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.
[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.

Product Documents

Purity:>98.00%Appearance:A solid
COASDSData Sheet

Chemical Properties

CAS No.
328968-36-1
Chemical Name
4-[(4Z)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid
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
Molecular Formula
C24H19N3O6
Molecular Weight
445.42
Solubility
≥ 11.1mg/mL in DMSO
Storage
Store at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

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