C646 is a selective and competitive histone acetyltransferase p300 inhibitor with Ki of 400 nM, and is less potent for other acetyltransferases.
For research use only. We do not sell to patients.
C646 Chemical Structure
CAS No. : 328968-36-1
This product is a controlled substance and not for sale in your territory.
Based on 63 publication(s) in Google Scholar
C646 purchased from MedChemExpress. Usage Cited in:
Biochem Pharmacol. 2023 Mar 11;210:115497.
[Abstract]
C646 (20 μM) decreases the expression of PLK1 following effective inhibition of H3K27ac, and αSMA and COLI are also repressed, in TGFβ-activated LX2 cells.
C646 purchased from MedChemExpress. Usage Cited in:
Cell Death Differ. 2018 Nov;25(11):1980-1995.
[Abstract]
Western blot analysis of LAMC2 expression after C646 treatment in KYSE150 and KYSE450. C646 treatment: 20μM, 12h.
C646 purchased from MedChemExpress. Usage Cited in:
Free Radic Biol Med. 2018 Aug 20;124:454-465.
[Abstract]
To explore whether P300 is required for NaB’s activation of Nrf2 expression and function, HG-treated endothelial cells (ECs) are co-treated with NaB, in the presence or absence of C646.
C646 purchased from MedChemExpress. Usage Cited in:
Eur J Pharmacol. 2017 Oct 5;812:206-215.
[Abstract]
C646 inhibits the proliferation of Cervical cancer cells and induced the accumulation of p53 protein. Protein levels of p53 and p21 are augmented by C646 in a dose-dependent manner. Whole cell lysates are analyzed with western-blot analysis.
C646 purchased from MedChemExpress. Usage Cited in:
Biochem Biophys Res Commun. 2016 Dec 2;481(1-2):90-96.
[Abstract]
DMKG inhibits autophagy of HSCs via acetyl-coenzyme A and EP300. Western blot analysis of LC3B, Beclin-1, a-SMA, and collagen-I expression from lysates of HSC-T6 incubated with control media, DMKG (4 mM), or Lipoic acid (5 mM) in the presence or absence of C646 (10 mM) for 12 h.
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CBP/p300 GCN5/PCAF TIP60 MOZ/MORF HBO1
Description
C646 is a selective and competitive histone acetyltransferase p300 inhibitor with Ki of 400 nM, and is less potent for other acetyltransferases[1].
IC50 & Target
CBP/p300
In Vitro
C646 is a linear competitive inhibitor of p300 versus acetyl-CoA with a Ki of 400 nM. C646 shows a noncompetitive pattern of p300 inhibition versus the H4-15 peptide substrate. C646 treatment reduces histone H3 and H4 acetylation levels and abrogates TSA-induced acetylation in cells. C646 has a more potent effect on cell growth than Lys-CoA-Tat does[1]. C646 enhances mitotic catastrophe after IR and suppresses phosphorylation of CHK1 after IRin A549 cells[2]. C646 attenuates the increased acetylation of GATA1 and the increased transcriptional activity of GATA1 induced by EDAG[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
C646 Related Antibodies
In Vivo
Suppression of P300 by c646 (intraperitoneally injected, 30 nmol/g/d for 2 weeks) dramatically reduces the level of blood glucose in db/db mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Fourteen-week-old male db/db mice and normal m/m mice[4]
Dosage:
30 nmol/g
Administration:
Intraperitoneally injected; daily; 2 weeks
Result:
The db/db mice showed greater body masses and higher levels of fasting blood glucose than the m/m mice.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
Solvent & Solubility
In Vitro:
DMSO : 13.89 mg/mL (31.18 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.2451 mL
11.2254 mL
22.4507 mL
5 mM
0.4490 mL
2.2451 mL
4.4901 mL
10 mM
0.2245 mL
1.1225 mL
2.2451 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 1.67 mg/mL (3.75 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 1.67 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (16.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 1.67 mg/mL (3.75 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 1.67 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (16.7 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[1]. Bowers EM, 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.
[Content Brief]
[2]. Oike T, 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.
[Content Brief]
[3]. Zheng WW, et al. EDAG positively regulates erythroid differentiation and modifies GATA1 acetylation through recruiting p300. Stem Cells. 2014 Aug;32(8):2278-89.
[Content Brief]
[4]. Zhen Fan, et al. Type 2 diabetes-induced overactivation of P300 contributes to skeletal muscle atrophy by inhibiting autophagic flux. Life Sci. 2020 Aug 10;258:118243.
[Content Brief]
[1]. Bowers EM, 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.
[2]. Oike T, 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.
[3]. Zheng WW, et al. EDAG positively regulates erythroid differentiation and modifies GATA1 acetylation through recruiting p300. Stem Cells. 2014 Aug;32(8):2278-89.
[4]. Zhen Fan, et al. Type 2 diabetes-induced overactivation of P300 contributes to skeletal muscle atrophy by inhibiting autophagic flux. Life Sci. 2020 Aug 10;258:118243.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
