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EPZ-6438 | EPZ-6438 : SAM competitive inhibitor of EZH2
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 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
EZH2
  • Ki:EZH2 2.5 nM
  • IC50:1.4-5.6 nM
SAM competitive
30-1,000 nM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
EPZ-6438 is 35-fold selective for EZH2 over EZH1 and 4,500-fold selective over all other protein met ...
Selectivity Assessment Description:
Not available
In Cell Selectivity Assessment
Potency Assay Off-Target:
No activity was detected by assessing other histone substrates (H3K9, H3K4, H3K36 and H3K79)

Potency
Cellular
In Vitro

EZH2

Mode of Action: SAM competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1073/pnas.1303800110

In Vivo Validations

Mouse
Dose: 125-500 mg/kg
Route of delivery: Oral
Organ of interest (O): G401 xenograft
Target engagement assay: Indirect, inhibition of substrate methylation in tumor

DOI Reference: 10.1073/pnas.1303800110

Orthogonal Probes def

GSK343
CPI-169
CPI-360

Chemical Information

Molecular Formula C34H44N4O4
SMILEs CCN(c1cc(-c2ccc(CN3CCOCC3)cc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)C1CCOCC1
InChI InChI=1S/C34H44N4O4/c1-5-38(29-10-14-41-15-11-29)32-20-28(27-8-6-26(7-9-27)22-37-12-16-42-17-13-37)19-30(25(32)4)33(39)35-21-31-23(2)18-24(3)36-34(31)40/h6-9,18-20,29H,5,10-17,21-22H2,1-4H3,(H,35,39)(H,36,40)
Molecular weight 572.34 Da
AlogP 4.73466
HBond acceptors 8
HBond donors 2
Atoms 86

References

Publications

Cross References

canSARChEMBLBindingDB

Vendors

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

Expert Reviews

by SERP
(on 15 Aug 2016 )
Cellular Use Rating
In Model Organisms
The compound shows good potency in the inhibition of H3K27 trimethylation in multiple cell lines, making it a potentially useful tool. Note that 4 days of dosing is required. Note also that the compound...
by SERP
(on 23 Dec 2016 )
Cellular Use Rating
In Model Organisms
This compound shows high in vitro potency for wild-type EZH2 (Ki = 2.5 nM) and for EZH2 mutations (Y641F, C, H, N, S and A677G); SAM competitive and non-competitive with peptide substrate; ca. 35-fold...
by SERP
(on 16 Jan 2017 )
Cellular Use Rating
In Model Organisms
EPZ-6438 is a potent, SAM-competitive inhibitor of wild-type and all known mutants of EZH2 with biochemical selectivity over EZH1 and other histone methyl transferases. Potent target engagement in cells...
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. Read more about our evaluation criteria