C646 |
Catalog No.GC12733
One-Click Copy Product Info
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Se ha demostrado que C646, un potente y selectivo inhibidor de la histona acetiltransferasa p300/CBP (Ki 400 nM), tiene actividad pleiotrópica, incluidos los efectos neuroprotectores, anticancerígenos y de transición mesenquimal antiepitelial (anti-EMT).
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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Se ha demostrado que C646, un potente y selectivo inhibidor de la histona acetiltransferasa p300/CBP (Ki 400 nM), tiene actividad pleiotrópica, incluidos los efectos neuroprotectores, anticancerígenos y de transición mesenquimal antiepitelial (anti-EMT) [1-4].
C646(10µM; 2 h) suprime la producción de citoquinas estimuladas por LPS[5]. C646(10-50 µM) inhibe la acetilación de la histona H3 y la proliferación de células cancerosas de páncreas [6]. C646(20 µM; 4 h) activa la señalización de insulina y aumenta la translocación de la membrana de los sustratos de proteínas del receptor de insulina (IRS) en ausencia de insulina en las células Hepa1-6[7].
C646(10 ul; una dosis por día; 7 días) alodinia mecánica atenuada e hiperalgesia térmica, acompañada de una expresión suprimida de COX-2 en la médula espinal[8]. El tratamiento C646(1 µg/gm; i.v;14 días) atenuó la acetilación p300 y H3K56 y mejoró la rigidez arterial y la reserva de flujo coronario (CFR) a través de la mejora de la disfunción de las células endoteliales (EC) y la supresión de 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.
| Experimentos celulares [1]: | |
Líneas celulares | Macrófagos derivados de la médula ósea del ratón (BMDMs) |
Método de preparación | En este ensayo, la producción de Ac-H4-15 marcado con 14C se monitorea electroforóricamente. Las reacciones se realizaron en 20 mM HEPES (pH 7.9), y contuvieron 5 mM DTT, 80 µM EDTA, 40 µg/ml BSA, 100 µM H4-15, y 5 nM p300. DMSO se mantuvo constante al 2.5%, , y los inhibidores (incluyendo C646) se examinaron a 25 µM. Las reacciones se incubaron a 30 C durante 10 minutos, se inició con la adición de una mezcla 1:1 de 12C-acetyl-CoA y 14C-acetyl-CoA a una concentración final de 20 µM, y se permitió ejercutar durante 10 minutos a 30 C. Luego, las reacciones se atenúan con la adición de un R14% de SDS (w/v). La rotación se mantuvo por debajo del 10%. |
Condiciones de reacción | 10µM；2 h |
Áreas de aplicación | C646 es un inhibidor competitivo de p300 con un Ki de 400 nM y es selectivo frente a otras acetiltransferasas. |
| Experimentos con animales [2]: | |
Modelos animales | Ratas macho de Sprague-Dawley (modelo de lesión por constricción crónica (CCI)) |
Método de preparación | Se administraron C646 a través del catéter intratecal lumbar. Las ratas tratadas con C646 recibieron C646 (10 ul, diluidas con 10% de DMSO, una dosis por día) de los días 7 a 14 después de la cirugía CCI . Después de que se administraran los vectores o medicamentos, el catéter se enjuagó con solución salina 5ul al 0.9%. |
Forma de dosificación | 10 ul; una dosis al día; 7 días |
Áreas de aplicación | C646 alodinia mecánica atenuada e hiperalgesia térmica, acompañada de una expresión suprimida de COX-2 en la médula espinal. |
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 |
| 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.)