EPZ011989

Inhibitor of EZH2, EZH1

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(2 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

EZH2
EZH1

Inhibitor

100-600 nM

DOI - 10.1021/acsmedchemlett.5b00037

Probe Availability:

In Vitro Validations

Uniprot ID: Q15910

Target Class: Epigenetic

Target SubClass: Protein methyltransferase

Potency: IC 50

Potency Value: 6 nM

Potency Assay: ELISA-based protein substrate methylation assay.

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

Structure-activity relationship: Yes.

Target aliases:

Histone-lysine N-methyltransferase EZH2, KMT6, EZH ...

DOI Reference: 10.1021/acsmedchemlett.5b00037

Uniprot ID: Q15910

Target Class: Epigenetic

Target SubClass: Protein methyltransferase

Potency: Ki

Potency Value: <3 nM

Potency Assay: Biochemical Assay

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

Target aliases:

Histone-lysine N-methyltransferase EZH2, KMT6, EZH ...

DOI Reference: 10.1021/acsmedchemlett.5b00037

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): 15-fold selective for EZH2 > EZH1 in protein substrate methylation assay. 3000-fold selective for EZH2 > 20 other protein methyltransferases (CARM1, DOT1L, EHMT1, EHMT2, PRMT1, PRMT3, PRMT5, PRMT6, PRMT8, SETD2, SETD7, SUV39H1, SMYD2, SMYD3, WHSC1, WHSC1L1).

Probe Selectivity in Vitro:

15-fold selective for EZH2 > EZH1 in protein substrate methylation assay. 3000-fold selective for EZH2 > 20 other protein methyltransferases (CARM1, DOT1L, EHMT1, EHMT2, PRMT1, PRMT3, PRMT5, PRMT6, PRMT8, SETD2, SETD7, SUV39H1, SMYD2, SMYD3, WHSC1, WHSC1L1).

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Users should note the salt and vehicle preparation for any in vivo use (0.5% methyl cellulose and 0.1% Tween-80 was used in original manuscript).

(last updated: 29 May 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This small molecule represents an additional probe for testing the effects of EZH2 inhibition in cells and in vivo. Oral bioavailability and improved metabolic stability are key features that add to its value for use as a probe. The concentration range in mouse models seems somewhat high, but given its clearance from plasma, this is required to maintain predicted efficacious levels in an animal. The lack of a negative control compound for direct comparison makes this compound less ideal than other EZH2 inhibitors currently available (especially UNC-1999).

(last updated: 20 Jun 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

This is a good tool compound for a couple of interesting targets. I'm not concerned by lack of a negative control compounds, since such compounds often offer a false confidence (if they lack the same off targets as their positive compounds).

(last updated: 17 Aug 2016 )