EI1

SAM competitive inhibitor of EZH2

Structure

Information

Protein target names: EZH2

Mechanism of action: SAM competitive inhibitor

Recommended in-cell concentration:
Up to 1 uM

In Vitro Validations

Uniprot ID: Q15910
Target Class: Epigenetic
Target SubClass: Protein methyltransferase
Potency: Ki
Potency Value: 13 nM
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Histone-lysine N-methyltransferase EZH2, KMT6, EZH ...

DOI Reference: 10.1073/pnas.1210371110

Uniprot ID: Q15910
Target Class: Epigenetic
Target SubClass: Protein methyltransferase
Potency: IC50
Potency Value: 15 nM
Potency Assay: PRC2 enzyme inhibition assays against wild-type EZH2
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Histone-lysine N-methyltransferase EZH2, KMT6, EZH ...

DOI Reference: 10.1073/pnas.1210371110

Uniprot ID: Q15910
Target Class: Epigenetic
Target SubClass: Protein methyltransferase
Potency: IC50
Potency Value: 13 nM
Potency Assay: PRC2 enzyme inhibition assays against Y641F EZH2.
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Histone-lysine N-methyltransferase EZH2, KMT6, EZH ...

DOI Reference: 10.1073/pnas.1210371110

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments


SERP Ratings

In Cell Rating

(last updated: 9 Sept 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

El1 is a promising inhibitor with good potency as a SAM competitive inhibitor against EZH2 at 13 nM. El1 was obtained from an initial high-throughput screen to identify the chemotype with the best properties. Optimization of this chemical series resulted in the identification of El1. Although no cell toxicity data were presented, the selectivity profile for El1 against EZH1 (which has >90% homology to EZH2) was greater than 90-fold. El1 also lacks selectivity for wild-type EZH2 over the Y641 EZH2 mutant. No information is presented regarding the pharmacokinetic profile for El1, but the structure seems to comply with the Rule of 5. The molecule should be available through a simple synthetic pathway without additional concerns (like sterocenters). As a functional probe, El1 blocks HMT activity of EZH2 without disrupting the chromatin binding of PRC2, with inhibition of cell proliferation and colony formation.

(last updated: 9 Sept 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

Cell-based activity is oberved at 3.3 uM.

(last updated: 10 Dec 2016 )