328968-36-1
328968-36-1 structure
- Name: C646
- Chemical Name: 4-[(4Z)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid
- CAS Number: 328968-36-1
- Molecular Formula: C24H19N3O6
- Molecular Weight: 445.424
- Catalog: Biochemical Inhibitor Epigenetics Histone Acetyltransferase inhibitor
- Create Date: 2017-06-27 05:54:18
- Modify Date: 2024-01-05 17:40:48
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C646 is a selective and competitive histone acetyltransferase p300 inhibitor with Ki of 400 nM, and is less potent for other acetyltransferases.
| Name | 4-[(4Z)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid |
|---|---|
| Synonyms |
Benzoic acid, 4-[(4Z)-4-[[5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl]methylene]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]-
4-[(4Z)-4-{[5-(4,5-Dimethyl-2-nitrophenyl)-2-furyl]methylene}-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid c646 qcr-235 |
| Description | C646 is a selective and competitive histone acetyltransferase p300 inhibitor with Ki of 400 nM, and is less potent for other acetyltransferases. |
|---|---|
| Related Catalog | |
| Target |
Ki: 400 nM (histone acetyltransferase 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 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]. |
| Kinase Assay | Reactions are carried out at 30°C for times varying from 2 to 4 min under the following reaction conditions: 50 mM HEPES, pH 7.9, 50 mM NaCl, 0.05 mg/mL BSA, 5 mM DTT, 0.05 mM EDTA, 0.25% DMSO, 10 μM of X. laevis histone H3, and varying concentrations of C646 (0, 3, 10 μM). The reactions contains either 70 nanograms of Rtt109/Vps75, 15 nanograms of yGcn5, 300 nanograms of the SAS complex or 1 microgram of hMOZ. The amount of enzyme used in each assay is estimated by comparing Coomassie Blue staining of samples with bovine serum albumin standards, analyzed by SDS-PAGE. The mixture is allowed to equilibrate at 30°C for 10 min before the reaction is initialed with addition of a 1:1 mixture of 12C-AcCoA and 14C-AcCoA to a final concentration of 20 μM. After the appropriate time the reaction is quenched with 6 X Tris-Tricine gel loading buffer which contains 0.2mol/LTris-Cl pH 6.8, 40% v/v glycerol, 14% w/v SDS, 0.3 mol/LDTT, and 0.06% w/v Coomassie Blue. The 14C-labeled histone substrates are separated from reactants on a 16.5% Tris-Tricine SDS-PAGE gel. The rate of 14C-incorporation into histone H3 is quantified by autoradiography. All assays are in duplicate, and these generally agree within 20%. |
| Cell Assay | Cells are seeded in 6-well plates, incubated at 37°C for 4-10 h for attachment, and exposed (or not) to C646. After incubation for 2 h, the cells are subjected (or not) to IR and incubated for 10 days for colony formation. The cells are fixed with methanol and stained with crystal violet. Colonies of at least 50 cells are counted. The surviving fraction is normalized to the corresponding controls. The dose required to reduce the surviving fraction to 10% (D10) of the irradiated cells is calculated by using the linear-quadratic model. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 662.6±65.0 °C at 760 mmHg |
| Melting Point | 224-226℃ |
| Molecular Formula | C24H19N3O6 |
| Molecular Weight | 445.424 |
| Flash Point | 354.5±34.3 °C |
| Exact Mass | 445.127380 |
| PSA | 128.93000 |
| LogP | 4.87 |
| Appearance | red to brown |
| Vapour Pressure | 0.0±2.1 mmHg at 25°C |
| Index of Refraction | 1.663 |
| Storage condition | 2-8°C |
| Water Solubility | DMSO: >25mg/mL |
