C646
C646 structure
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Common Name | C646 | ||
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| CAS Number | 328968-36-1 | Molecular Weight | 445.424 | |
| Density | 1.4±0.1 g/cm3 | Boiling Point | 662.6±65.0 °C at 760 mmHg | |
| Molecular Formula | C24H19N3O6 | Melting Point | 224-226℃ | |
| MSDS | Chinese USA | Flash Point | 354.5±34.3 °C | |
| Symbol |
GHS09 |
Signal Word | Warning | |
Use of C646C646 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 |
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| Synonym | More Synonyms |
| Description | C646 is a selective and competitive histone acetyltransferase p300 inhibitor with Ki of 400 nM, and is less potent for other acetyltransferases. |
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| 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 of Characters | 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 |
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Sp3/REST/HDAC1/HDAC2 Complex Represses and Sp1/HIF-1/p300 Complex Activates ncx1 Gene Transcription, in Brain Ischemia and in Ischemic Brain Preconditioning, by Epigenetic Mechanism.
J. Neurosci. 35 , 7332-48, (2015) The Na(+)-Ca(2+) exchanger 1 (NCX1) is reduced in stroke by the RE1-silencing transcription factor (REST), whereas it is increased in ischemic brain preconditioning (PC) by hypoxia-inducible factor 1 ... |
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P300-dependent STAT3 acetylation is necessary for angiotensin II-induced pro-fibrotic responses in renal tubular epithelial cells.
Acta Pharmacol. Sin. 35(9) , 1157-66, (2014) To explore the signal transducer and activator of transcription 3 (STAT3) signaling pathway, especially STAT3 acetylation, in angiotensin II (Ang II)-induced pro-fibrotic responses in renal tubular ep... |
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Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity.
Sci. Rep. 5 , 17395, (2015) Glucokinase (GK), mainly expressed in the liver and pancreatic β-cells, is critical for maintaining glucose homeostasis. GK expression and kinase activity, respectively, are both modulated at the tran... |
| 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 |