C646
C646, a pyrazolone-containing small molecule, is a cell-permeable histone acetyltransferase (HAT) inhibitor that competitively and selectively inhibits the HAT activity of p300, a transcriptional co-activator involved in a variety of gene regulatory pathways and protein acetylation events, with the inhibition constant Ki value of 400 nM and the half maximal inhibition concentration IC50 value of 1.6 μM [1].
C646 binds to p300 as the Z-isomer forming hydrogen bonds between Thr1411, tYR1467, Trp1466 and Arg1410 on the side chains of p300 and oxygen atoms of C646 [1].
C646 is also capable of inhibiting a variety of p300 HAT mutants, including T1411A, Y1467F, W1466F and R1410A with IC50 values of 3.4 μM, 7 μM, 5 μM and 2.5 μM respectively [1].
Reference
References:
[1] Bowers EM, Yan G, Mukherjee C, Orry A, Wang L, Holbert MA, Crump NT, Hazzalin CA, Liszczak G, Yuan H, Larocca C, Saldanha SA, Abagyan R, Sun Y, Meyers DJ, Marmorstein R, Mahadevan LC, Alani RM, Cole PA. 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.
- 1. Jin-Man Kim, Ho Kyoung Kim, et al. "Extracellular C1qbp inhibits myogenesis by suppressing NFATc1." Sci Rep. 2024 Jul 8;14(1):15678 PMID: 38977785
- 2. Jiang W, Yuan X, et al. "Inhibition of Histone H3K27 Acetylation Orchestrates Interleukin-9-Mediated and Plays an Anti-Inflammatory Role in Cisplatin-Induced Acute Kidney Injury." Front Immunol. 2020;11:231. PMID:32194547
- 3. Li N, Yang L, et al. "BET bromodomain inhibitor JQ1 preferentially suppresses EBV-positive nasopharyngeal carcinoma cells partially through repressing c-Myc." Cell Death Dis. 2018 Jul 9;9(7):761. PMID:29988031
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 445.42 |
| Cas No. | 328968-36-1 |
| Formula | C24H19N3O6 |
| Solubility | insoluble in H2O; ≥11.14 mg/mL in DMSO; ≥3.29 mg/mL in EtOH with ultrasonic |
| Chemical Name | 4-[(4Z)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid |
| SDF | Download SDF |
| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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Radioactive assay |
IC50 values for the putative p300 HAT inhibitors are determined using the direct radioactive assay described above. Reactions are performed in 20 mM HEPES (pH 7.9), and contained 5 mM DTT, 80μM EDTA, 40μg/ml BSA, 100μM H4-15, and 5 nM p300. Putative inhibitors are added over a range of concentrations, with DMSO concentration kept constant ( |
| Cell experiment [2]: | |
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Cell lines |
RAW264.7 murine macrophages |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1, 5, 10, 15, 20, 25 or 30 μM for 16 hr; 15 or 30μM for 6 h, or at 30μM for 20 h |
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Applications |
C646 decreased pro-inflammatory gene expression and NF-kB activity and inhibited histone deacetylases in RAW264.7 murine macrophages. Moreover, C646 decreased α-tubulin acetylation in RAW264.7 cells. |
| Animal experiment [3]: | |
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Animal models |
C57BL/6 male mice model |
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Dosage form |
2×0.75 μl injection volume in each case, 1.5 μg, administered over 2 min |
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Applications |
Inhibition of p300 by C646 in the infralimbic prefrontal cortex (ILPFC) enhanced the formation of fear extinction memory. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1Bowers, E. M., Yan, G., Mukherjee, C., Orry, A., Wang, L., Holbert, M. A., Crump, N. T., Hazzalin, C. A., Liszczak, G., Yuan, H., Larocca, C., Saldanha, S. A., Abagyan, R., Sun, Y., Meyers, D. J., Marmorstein, R., Mahadevan, L. C., Alani, R. M. and Cole, P. A. (2010) Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Chem Biol. 17, 471-4822 2van den Bosch, T., Boichenko, A., Leus, N. G., Ourailidou, M. E., Wapenaar, H., Rotili, D., Mai, A., Imhof, A., Bischoff, R., Haisma, H. J. and Dekker, F. J. (2016) The histone acetyltransferase p300 inhibitor C646 reduces pro-inflammatory gene expression and inhibits histone deacetylases. Biochem Pharmacol. 102, 130-140 3Marek, R., Coelho, C. M., Sullivan, R. K., Baker-Andresen, D., Li, X., Ratnu, V., Dudley, K. J., Meyers, D., Mukherjee, C., Cole, P. A., Sah, P. and Bredy, T. W. (2011) Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300. J Neurosci. 31, 7486-7491 |
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| Description | C646 is an inhibitor of p300 with a Ki value of 400 nM. | |||||
| Targets | p300/CBP | |||||
| IC50 | 400 nM(Ki) | |||||
Quality Control & MSDS
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Chemical structure
Related Biological Data
Related Biological Data
