C646

Catalog No.S7152 Batch:S715202

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Technical Data

Formula

C24H19N3O6
Molecular Weight 445.42 CAS No. 328968-36-1
Solubility (25°C)* In vitro DMSO 13 mg/mL (29.18 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description C646 is an inhibitor for histone acetyltransferase, and inhibits p300 with a Ki of 400 nM in a cell-free assay. Preferentially selective for p300 versus other acetyltransferases. C646 induces cell cycle arrest, apoptosis and autophagy.
Targets
p300/CBP [1]
(Cell-free assay)
400 nM(Ki)
In vitro C646 is an inhibitor for histone acetyltransferase, inhibits p300 with a Ki of 400 nM and is selective versus other acetyltransferases. C646 produces 86% inhibition of p300 in vitro at 10 μM. C646 is a classical reversible p300 inhibitor. C646 treatment (25μM) reduces histone H3 and H4 acetylation levels and abrogates TSA-induced acetylation in cells. [1] C646 (20μM) induces apoptosis in androgen-sensitive and castration-resistant prostate cancer cell lines by interfering with AR and NF-kB pathways. [2] C646 blocks dynamic acetylation of H3K4me3 globally in mouse and fly cells, and locally across the promoter and start-site of inducible genes in the mouse, thereby disrupting RNA polymerase II association and the activation of these genes. [3]
In vivo C646 infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. [4] C646 attenuates mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord. [5]
Features Extensively used as a pharmacologic probe in cancer cells. Potential use for prostate and lung cancers.

Protocol (from reference)

Kinase Assay:[1]
  • 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 (<5%). Reactions are incubated at 30°C for 10 min, then initiated with addition of a 1:1 mixture of 12C-acetyl-CoA and 14C-acetyl-CoA to 20 mM. After 10 min at 30°C, reactions are quenched with 14% SDS (w/v). All concentrations are screened in duplicate. Gels are run, washed, dried, and exposed to a PhosphorImager plate, and production of Ac-H4-15 quantified to obtain IC50s.
Cell Assay:[1]
  • Cell lines

    C3H10T1/2

  • Concentrations

    ~25 μM

  • Incubation Time

    1 to 3 hr

  • Method

    Histone acetylation assays in mouse cells. C3H10T1/2 mouse fibroblasts are grown in DMEM with 10% FCS at 37°C with 6% CO2. Confluent cultures are rendered quiescent in DMEM with 0.5% FCS for 18-20 hr prior to treatment. Cells are treated with the following compounds: TSA (10 ng/ml [33 nM]), C646 (25 μM), C37 (25 μM). Antibodies are used at the following concentrations: total H3 (1:10000; ab7834; Abcam); H4K12ac (1:2500; 06-761; Upstate). Rabbit anti-H3K9ac (1:10000) antibodies are generated in-house. Histones are isolated from cells by acid extraction, separated by SDS and acid-urea polyacrylamide gel electrophoresis and analyzed by western blotting.
Animal Study:[4]
  • Animal Models

    mouse

  • Dosages

    2×0.75 μl injection volume in each case, 1.5 μg, administered over 2 min

  • Administration

    infusion into ILPFC

References

  • https://pubmed.ncbi.nlm.nih.gov/20534345/
  • https://pubmed.ncbi.nlm.nih.gov/21709130/
  • https://pubmed.ncbi.nlm.nih.gov/21518915/
  • https://pubmed.ncbi.nlm.nih.gov/21593332/
  • https://pubmed.ncbi.nlm.nih.gov/23176208/

Customer Product Validation

Phosphorylation of STAT6 in butyrate-treated M2-BMDMs. Western blotting was performed with anti-phospho-STAT6, STAT6, and β-actin. Data are representative of three independent experiments. M2:M2 macrophage; But:butyrate.

Data from [ , , Sci Rep, 2016, 6:24838. ]

A. Immunoprecipitation of HSP90 from NT, shHSF1 or shHSF1 Mec-1 cells treated with 20 μM, C646 for 24 hours followed by immunoblotting for acetyl lysine and HSP90 (top panel). Immunoprecipitation of CDC37 followed by immunoblot analysis of HSP90 and the indicated HSP90 client kinases (bottom panel).

Data from [ , , Oncotarget, 2015, 6(31):31767-79. ]

(E) si-P300-3 and C646 separately suppressed the Res-induced mRNA expression of VEGFb, VEGFR1, and VEGFR2 in differentiated PC-12 cells (*P<0.05, **P<0.01, ***P<0.01).

Data from [ , , Front Neurosci, 2018, doi:10.3389/fnins.2018.00341 ]

Left: The protein level of acH4K5 in the DMSO and C646 5 µM groups. H4 was used as a loading control. Right: The expression level of cyclin D3 decreased in the C646 5 µM group compared with the DMSO group detected by Western blotting analysis. Protein lysates for Western blot analysis were obtained at 48 h after C646 treatment.

Data from [ , , Biol Reprod, 2015, 93(1): 13 ]

Selleck's C646 Has Been Cited by 124 Publications

TIGIT deficiency promotes autoreactive CD4+ T-cell responses through a metabolic‒epigenetic mechanism in autoimmune myositis [ Nat Commun, 2025, 16(1):4502] PubMed: 40374622
Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells [ Nat Commun, 2025, 16(1):524] PubMed: 39789010
Extracellular Histones as Exosome Membrane Proteins Regulated by Cell Stress [ J Extracell Vesicles, 2025, 14(2):e70042] PubMed: 39976275
Loss of p300 in proximal tubular cells reduces renal fibrosis and endothelial-mesenchymal transition [ EMBO Mol Med, 2025, 17(7):1575-1598] PubMed: 40588562
Lactylation modification of HIF-1α enhances its stability by blocking VHL recognition [ Cell Commun Signal, 2025, 23(1):364] PubMed: 40760493
Herbal-based Xuebijing injection ameliorated vascular endothelial dysfunction via inhibiting ACLY/MYB/RIG-I axis in sepsis-associated lung injury [ Phytomedicine, 2025, 140:156573] PubMed: 40088739
Nuclear PD-L1 triggers tumour-associated inflammation upon DNA damage [ EMBO Rep, 2025, 10.1038/s44319-024-00354-9] PubMed: 39747659
Histone acetylation facilitates multidirectional pulp repair through Neuregulin-1 mobilization [ Stem Cells Transl Med, 2025, 14(7)szaf022] PubMed: 40580029
Knockdown of ACC1 promotes migration and invasion of U251 glioma cells by epigenetically suppressing SDH [ Int J Oncol, 2025, 67(3)73] PubMed: 40747663
Ureaplasma urealyticum GrpE protein elicits glycolysis-mediated inflammatory responses through TLR2 in macrophages [ Immunobiology, 2025, 230(3):152902] PubMed: 40273504

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.