C646

Catalog No.S7152 Batch:S715203

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Technical Data

Formula

C24H19N3O6
Molecular Weight 445.42 CAS No. 328968-36-1
Solubility (25°C)* In vitro DMSO 23 mg/mL (51.63 mM)
Water Insoluble
Ethanol Insoluble
* <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.)

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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

Customer Product Validation

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

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

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

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

Selleck's C646 has been cited by 108 publications

Acetylation-dependent regulation of core spliceosome modulates hepatocellular carcinoma cassette exons and sensitivity to PARP inhibitors [ Nat Commun, 2024, 15(1):5209] PubMed: 38890388
Musashi-2 potentiates colorectal cancer immune infiltration by regulating the post-translational modifications of HMGB1 to promote DCs maturation and migration [ Cell Commun Signal, 2024, 22(1):117] PubMed: 38347600
Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis [ Antioxidants (Basel), 2024, 13(4)424] PubMed: 38671872
Type II Interleukin-4 Receptor Activation in Basal Breast Cancer Cells Promotes Tumor Progression via Metabolic and Epigenetic Modulation [ Int J Mol Sci, 2024, 25(9)4647] PubMed: 38731867
Type II Interleukin-4 Receptor Activation in Basal Breast Cancer Cells Promotes Tumor Progression via Metabolic and Epigenetic Modulation [ Int J Mol Sci, 2024, 25(9)4647] PubMed: 38731867
LINC00355 promotes gastric carcinogenesis by scaffolding p300 to activate CDC42 transcription and enhancing HNRNPA2B1 to stabilize CDC42 mRNA dependent on m6A [ Mol Carcinog, 2024, 63(3):430-447] PubMed: 37983727
Pharmacological inhibition of p300 ameliorates steatosis, inflammation, and fibrosis in mice with non-alcoholic steatohepatitis [ Heliyon, 2024, 10(9):e30908] PubMed: 38774067
Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro [ PLoS Negl Trop Dis, 2024, 18(8):e0012428] PubMed: 39159234
Activation of lncRNA DANCR by H3K27 acetylation regulates proliferation of colorectal cancer cells [ Discov Oncol, 2024, 15(1):249] PubMed: 38940959
NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation [ bioRxiv, 2024, 2024.02.22.581432] PubMed: 38464226

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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.