A-395 A Chemical Probe For EED

This probe and its inactive control are available from Sigma (A-395 and A-395N) and Cayman (A-395).

A-395A-395N (negative control)

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.

in vitro potency

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)

A-395A-395N (negative control)
Physical and chemical properties for A-395
Molecular weight486.2
Molecular formulaC26H35FN4O2S
IUPAC name1-(5-fluoro-bicyclo[4.3.0]nona-1,3,5-trien-7-yl)-N,N-dimethyl-4-(4-(4-methylsulfonyl-piperazin-1-yl)-phenyl)-pyrrolidin-3-amine
No. of chiral centres3
No. of rotatable bonds5
No. of hydrogen bond acceptors7
No. of hydrogen bond donors0
Physical and chemical properties for A-395N
Molecular weight



Molecular formulaC24H34N4O2S
IUPAC name1-benzyl-N,N-dimethyl-4-(4-(4-methylsulfonyl-piperazin-1-yl)-phenyl)-pyrrolidin-3-amine
No. of chiral centres2
No. of rotatable bonds6
No. of hydrogen bond acceptors7
No. of hydrogen bond donors0
  • A-395: CN(C)[C@H]1CN(C[C@@H]1c1ccc(cc1)N1CCN(CC1)S(C)(=O)=O)C1CCc2cccc(c12)F
  • A-395N: CN(C)[C@@H]1CN(Cc2ccccc2)C[C@H]1c1ccc(cc1)N1CCN(CC1)S(C)(=O)=O
  • InChI:
  • InChIKey:
selectivity profile


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

in vitro potency
cell based assay data
pk properties
co-crystal structures

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Main features

synthetic schemes
materials and methods