EED226

EED226 : Allosteric inhibitor of EED

Structure

SERP Rating

In Cells

(4 ratings)

In Model Organisms

(3 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

Allosteric

100 nM - 1 uM

Probe Availability:

In Vitro Validations

Uniprot ID: O75530

Target Class: Epigenetic

Target SubClass: Polycomb family

Potency: Kd

Potency Value: 82 nM

Potency Assay: Isothermal titration calorimetry (ITC)

PDB ID for probe-target interaction (3D structure): 5GSA

Structure-activity relationship: Not available

Target aliases:

Polycomb protein EED, EED, EED_HUMAN, WAIT-1, hEED ...

DOI Reference: 10.1038/nchembio.2304

Uniprot ID: O75530

Target Class: Epigenetic

Target SubClass: Polycomb family

Potency: IC50

Potency Value: 23.4 nM

Potency Assay: In in vitro enzyme assays

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Polycomb protein EED, EED, EED_HUMAN, WAIT-1, hEED ...

DOI Reference: 10.1038/nchembio.2304

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): EED226 had limited activity against 21 protein methyltransferases (IC50 >100 uM). EED226 inhibited EZH1-PRC2 complex.

Probe Selectivity in Vitro:

EED226 had limited activity against 23 kinases (IC50 >10 uM), and 22 GPCRs, ion channels, nuclear receptors (IC50 >30 uM).

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

The fact that this compound is non-competitive with respect to SAM and peptide substrate is supported by an X-ray structure and enzymatic competition assays. The furane ring with electron-donating group is supposed to be unstable, but the structure was confirmed to be stable under even an acidic condition reported in the supplementary note. I think the chemical probe could prove to be very interesting and useful.

(last updated: 13 Jun 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This allosteric inhibitor of PRC2 competes with the H3K27me3 peptide for binding to EED. So far, it seems to be a very clean inhibitor. The only data on this compound has been published by a single group, so validation by other groups will increase enthusiasm for its use as an orthogonal inhibitor to SAM-competitive EZH2 inhibitors now in clinical trials.

(last updated: 14 Jun 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 16 Jun 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 29 Aug 2017 )