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A-395 | A-395 : Inhibitor of Protein-Protein Interaction of EED
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
EED
  • Ki:0.4 nM
  • IC50:90 nM (H3K27me3)
  • IC50:390 nM (H3K27me1/2)
Protein-Protein Interaction
100-300 nM

Selectivity

In Vitro Selectivity Assessment

Potency: Ki, Tm

Potency Assay Off-Target:
We assessed A-395's activity against 32 epigenetic methyltransferases by Scintillation proximity ass ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
A395 had no detectable impact on histone acetyltransferase activity.

Potency
Cellular
In Vitro

EED

Mode of Action: Protein-Protein Interaction

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1038/nchembio.2306

In Vivo Validations

Mouse
Dose: 300 mg/kg (with extended release vehicle)
Route of delivery: Subcutaneous
Organ of interest (O): Pfeiffer xenograft
Target engagement assay: Indirect, decrease in H3K27m3.

DOI Reference: 10.1038/nchembio.2306

Negative Control Compounds

A-395N

Orthogonal Probes def

EED226
UNC1999
GSK126

Chemical Information

Molecular Formula C26H35FN4O2S
SMILEs CN(C)[C@H]1CN(C2CCc3cccc(F)c32)C[C@@H]1c1ccc(N2CCN(S(C)(=O)=O)CC2)cc1
InChI InChI=1S/C26H35FN4O2S/c1-28(2)25-18-30(24-12-9-20-5-4-6-23(27)26(20)24)17-22(25)19-7-10-21(11-8-19)29-13-15-31(16-14-29)34(3,32)33/h4-8,10-11,22,24-25H,9,12-18H2,1-3H3/t22-,24?,25+/m1/s1
Molecular weight 486.25 Da
AlogP 0.0
HBond acceptors 6
HBond donors --
Atoms 69
PAINS * Yes

* This is an automated alert only, and may not necessarily indicate an issue with this probe. ( Learn more about PAINS )

References

Publications

Cross References

canSARChEMBLBindingDBBindingDBPubMed

Vendors

Note: This is not an exhaustive list and does not indicate endorsement by the portal.

Expert Reviews

by SERP
(on 27 Mar 2017 )
Cellular Use Rating
In Model Organisms
A-395 associates tightly to EED in a 1:1 binding model with a KD value of 1.5 nM (shown by SPR). A-395 inhibits the trimeric PRC2 complex (EZH2–EED–SUZ12) with an IC50 of 18 nM using a radioactivity-based...
by SERP
(on 12 Jul 2017 )
Cellular Use Rating
This compound closely phenocopies EZH2 enzyme inhibitors, which are better-characterized and have greater in vivo utility. Therefore, this would be an alternative choice for EZH2 inhibitor-resistant...
by SERP
(on 16 Aug 2017 )
Cellular Use Rating
In Model Organisms
A-395 is a potent and selective inhibitor of EED/PRC2 interaction (SPR Kd=1.5 nM, 1:1 EED/A-395 binding; Ki=0.5 nM). Calculated physicochemical properties: MW=486.65, PSA=55.5, AlogP=3.37, clogD pH...
A-395 is a very potent and selective inhibitor of EED/PRC2 interaction (SPR Kd 1.5 nM, 1:1 EED/A-395 binding; Ki 0.5 nM). Calculated physicochemical properties: MW 486.65, PSA 55.5, AlogP 3.37, clogD...
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