A-395

SKU: orb1310033

Description

A-395 is a potent small molecule antagonist that disrupts the protein-protein interactions within the PRC2 complex, specifically inhibiting the EZH2-EED-SUZ12 trimer with an IC50 of 18 nM. It is a valuable chemical probe for studying PRC2 biology in epigenetic research, applicable in both in vitro biochemical assays and cellular studies.

Research Area

Epigenetics & Chromatin

Key Properties

• CAS Number: 2089148-72-9
• MW: 486.65
• Purity: 98.43% (May vary between batches)
• Formula: C₂₆H₃₅FN₄O₂S
• SMILES: CN(C)[C@H]1CN(C[C@@H]1c1ccc(cc1)N1CCN(CC1)S(C)(=O)=O)C1CCc2cccc(F)c12
• Target: Histone Methyltransferase
• Solubility: 10% DMSO+40% PEG300+5% Tween-80+45% Saline:1 mg/mL (2.05 mM);DMSO:100 mg/mL (205.49 mM)

Bioactivity

• Target IC50:
  PRC2:18 nM
• In Vitro:
  The embryonic ectoderm development (EED) protein is an essential subunit of PRC2. A-395 antagonizes the H3K27me3 binding functions of EED by binding to the H3K27me3-binding pocket, thereby preventing the allosteric activation of PRC2's catalytic activity. A-395 competes for H3K27me3 peptide binding to EED (IC50: 7 nM) and selectively modulates PRC2 activity in cells, markedly reducing the H3K27 methyl mark. A-395 inhibits H3K27me2 and H3K27me3 (IC50s: 390 nM and 90 nM, respectively) and induces growth inhibition in human tumor cell lines sensitive to SAM-competitive EZH2 inhibitors, unlike its close chemical analog A-395N.
• Cell Research:
  1,000 multiple myeloma cells are seeded in each well of 96-well cell culture plates and treated with A-395 (0.001-100 μM) or DMSO control for 10 d before the cell proliferation assay. Cell proliferation assays are conducted with the CellTiter-Glo Luminescent Cell Viability Assay.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

A 395, A395, A-395, inhibit, Inhibitor, HistoneMethyltransferase, Histone Methyltransferase, PRC2

Compound Identifiers

PubChem CID

123132213