C-646

SKU: orb1305465

Description

C646 is a potent, selective, and competitive inhibitor of the histone acetyltransferase p300 (Ki=400 nM). It functions as an apoptosis inducer and radiosensitizer, with research applications in oncology for studying epigenetic mechanisms in both cellular and animal models.

Research Area

Cell Biology, Epigenetics & Chromatin, Neuroscience

Key Properties

• CAS Number: 328968-36-1
• MW: 445.4
• Purity: >98%
• Formula: C₂₄H₁₉N₃O₆
• SMILES: CC1=NN(C(=O)C1=Cc1ccc(o1)-c1cc(C)c(C)cc1[N+]([O-])=O)c1ccc(cc1)C(O)=O
• Target: Acetyltransferase
• Solubility: Soluble in DMSO (up to 10 mg/ml).

Bioactivity

• Target IC50:
  p300/CBP:400 nM (Ki)
• In Vivo:
  In vitro, C646 at a concentration of 10 μM inhibits p300 by 86%. In castration-sensitive androgen-responsive prostate cancer cell lines, C646 (20 μM) induces apoptosis by interfering with the AR and NF-kB pathways. Furthermore, C646 at 25 μM reduces the acetylation levels of histones H3 and H4 and blocks TSA-induced acetylation. In mouse cells, C646 inhibits the dynamic acetylation of all H3K4me3, spanning locally across promoters and transcription start sites of inducible genes, thereby disrupting the interaction with RNA polymerase II and the activation of these genes.
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• In Vitro:
  In the spinal cord, C646 can attenuate mechanical and thermal hyperalgesia, accompanied by the suppression of COX-2 expression. When administered immediately after weak extinction training into the ILPFC, C646 enhances the integration of fear extinction memory.
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• Cell Research:
  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.(Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

EpigeneticReaderDomain, Epigenetic Reader Domain, HistoneAcetyltransferase, Histone Acetyltransferase, HATs, HAT, inhibit, Inhibitor, C646, C-646, C 646, Autophagy, Apoptosis, p300/CBP

Compound Identifiers

PubChem CID

2871948