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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

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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

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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