EPZ005687

EPZ005687 : SAM competitive of EZH2

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 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.

Probe EPZ005687 is in the process of SERP review.

Please continue to check back for new reviews and commentary.

Information

EZH2 (Mutant:EZH2 WT, EZH2 Y641F, EZH2 A677G)

SAM competitive

up to 1 uM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: Q15910

Target Class: Epigenetic

Target SubClass: Methyltransferase

Potency: Ki

Potency Value: 24 ± 7 nM

Potency Assay: Biochemical Enzyme Assay

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

Target aliases:

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

DOI Reference: 10.1038/nchembio.1084

Uniprot ID: Q15910

Target Class: Epigenetic

Target SubClass: Methyltransferase

Potency: IC50

Potency Value: 54 ± 5 nM

Potency Assay: Flashplate assay

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

Target aliases:

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

DOI Reference: 10.1038/nchembio.1084

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): EPZ005687 showed ∼50-fold selectivity for EZH2 over EZH1-containing PRC2. EPZ005687 was tested against a panel of 15 other human PMTs and 6 EZH2 enzymes with point mutations in the SET domain at Tyr641 or Ala677. EPZ005687 had >500-fold selectivity against all of the tested PMTs, with the exception of the closely related PRC2 complex containing EZH1 in place of EZH2. Outside target family: EPZ005687 was evaluated by measuring its ability to displace radioligands from 77 human ion channels and G protein–coupled receptors at a concentration of 10 μM. Four targets were displaced by more than 50% , and the lowest IC50 extrapolated for any of these targets was 1.5 μM, indicating a selectivity of >60-fold.

Potency assay, off target (cells): 5.6 µM

Probe Selectivity in Cell:

Western blot assessing different histone marks; histones were isolated from cells after treatment with or without a high con- centration of EPZ005687 (5.6 μM) for 4 d and probed for a broad panel of histone post-translational modifications (K27 me3, K27me2, K27me1, K27ac, K4me3, K9me3, K36me2, K79me2). The only histone methyl marks decreased by compound treatment are those at H3K27.

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 2 Feb 2023 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

This is a highly selective probe with a high potency in biochemical assays as well as in lymphoma cell lines. The probe shows a dose depended efficacy on mutated lymphoma cell lines but spares the wild type.

(last updated: 17 Jun 2024 )