This probe and its inactive control are available from Sigma (A-395 and A-395N).
For any inquiries please contact firstname.lastname@example.org.
A collaboration between Abbvie and the SGC has resulted in the discovery of A-395, the first potent and selective chemical probe for EED. The in vitro activity of A-395 includes potent binding to EED with Ki = 0.4 nM, inhibits the PRC2 complex with IC50 = 34 nM for methylation of H3K27 and greater than 100-fold selectivity over other histone methyltransferases and non-epigenetic targets. In cellular assays, A-395 inhibits the PRC2 complex (thus inhibiting the formation of H3K27me3) with IC50 = 90 nM (RD rhabdoid tumor cell line; 3 days).
A closely related compound, A-395N, exhibits no activity in the biochemical and cellular assays, and is an ideal control compound for cellular studies.
A-395 potently inhibited the formation of H3K27me3 (via antagonizing EED in the trimeric PRC2 complex (EZH2:EED:SUZ12)) with IC50 = 34 ± 2 nM (Hill Slope = 0.7)
Physical and chemical properties for A-395
No. of chiral centres
No. of rotatable bonds
No. of hydrogen bond acceptors
No. of hydrogen bond donors
Physical and chemical properties for A-395N
Selectivity of A-395 against 32 methyltransferase enzymes
Selectivity of a) A-395 and b) A-395N relative to epigenetic readers using a thermal shift assay
A-395 inhibits the activity of the PRC2 complex in cells – high-content screening assay of RD Rhabdoid tumor cell line treated for 72 hours
1. Binding of A-395 to EED
2. Close-up shot of A-395 showing H-bonds.
3. A-395 superimposed with structure of PRC2 complex with Jarid2 peptide (EED site) and H3K27M in EZH2 catalytic site. EED in blue, EZH2 in gray, and SUZ12 in yellow.
4. Close-up of overlay of A-395 with Jarid2 peptide in PRC2 complex.
Yupeng He, Sujatha Selvaraju, Michael L Curtin, et al. The EED protein–protein interaction inhibitor A-395 inactivates the PRC2 complex . Nature Chem. Biol.(2017)