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JQEZ5 | JQEZ5 : 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 (Mutant:WT, Y641N, Y641F, Y641C)
  • EZH2:11 nM
  • Kd:87 nM
  • IC50:2500 nM
SAM competitive
up to 10 uM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
Limited activity against 22 Protein methyltransferases
Selectivity Assessment Description:
Not available

Potency
Cellular
In Vitro

EZH2 (Mutant:WT, Y641N, Y641F, Y641C)

Mode of Action: SAM competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1038/nm.4092

In Vivo Validations

Mouse
Dose: 5 mg/Kg IV, 10 mg/Kg PO, 75 mg/Kg IP
Route of delivery: Intraperitoneal, Intravenous, Oral
Plasma half life: 3.9 hr (IP)
Systemic clearance: 2.4 L/h/kg IV
Cmax: 15 uM IP
Bioavailability: 33% PO
Volume of Distribution at Steady-State: 2.3 L/Kg IV

Reference: --

Negative Control Compounds

JQEZ23
Notes: JQEZ23 had little inhibitory activity toward purified PRC2

Orthogonal Probes def

GSK343
CPI-360
EPZ-6438

Chemical Information

Molecular Formula C30H38N8O2
SMILEs CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccc(N3CCN(C)CC3)nc2)nc2c1cnn2C(C)C
InChI InChI=1S/C30H38N8O2/c1-6-7-21-14-20(4)34-30(40)24(21)17-32-29(39)23-15-26(35-28-25(23)18-33-38(28)19(2)3)22-8-9-27(31-16-22)37-12-10-36(5)11-13-37/h8-9,14-16,18-19H,6-7,10-13,17H2,1-5H3,(H,32,39)(H,34,40)
Molecular weight 542.31 Da
AlogP 3.7052200000000024
HBond acceptors 10
HBond donors 2
Atoms 78

References

Publications

Cross References

canSARChEMBLBindingDB

Vendors

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Expert Reviews

by SERP
(on 3 Aug 2016 )
Cellular Use Rating
In Model Organisms
An evaluation of the selectivity of this compound for other targets is missing. Due to the close structural analogy with other known EZH2 inhibitors (UNC1999 and GSK343) that showed no off-target activity...
by SERP
(on 11 Sept 2016 )
Cellular Use Rating
In Model Organisms
SAR data are not presented but could presumably have been as other analogs were made. The level of in vitro cellular activity (viability) is relatively low (50% reduction, Fig 6D) given that the compound...
by SERP
(on 15 Jun 2017 )
Cellular Use Rating
In Model Organisms
( The reviewer did not leave any comments )
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