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UNC1999 | UNC1999 : Inhibitor of EZH2 and EZH1
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (2 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
  • IC 50:10 nM
  • Ki:4.6 nM.
  • IC 50:124 nM
EZH1
  • IC 50:45 nM
  • IC50:124 nM
Inhibitor
up to 400 nM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
UNC1999 is 10,000-fold selective for EZH2 over 15 other lysine, arginine or DNA methyltransferases.
Selectivity Assessment Description:
UNC1999 is 10,000-fold selective for EZH2 over 15 other lysine, arginine or DNA methyltransferases. ...

Potency
Cellular
In Vitro

EZH2

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/cb400133j

EZH1

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/cb400133j

In Vivo Validations

Mouse
Dose: 15, 50 or 150 mg/kg
Route of delivery: Intraperitoneal

DOI Reference: 10.1021/cb400133j

Negative Control Compounds

UNC2400

Orthogonal Probes def

GSK343
CPI-169
EPZ011989

Chemical Information

Molecular Formula C33H43N7O2
SMILEs CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccc(N3CCN(C(C)C)CC3)nc2)cc2c1cnn2C(C)C
InChI InChI=1S/C33H43N7O2/c1-7-8-24-15-23(6)37-33(42)28(24)19-35-32(41)27-16-26(17-30-29(27)20-36-40(30)22(4)5)25-9-10-31(34-18-25)39-13-11-38(12-14-39)21(2)3/h9-10,15-18,20-22H,7-8,11-14,19H2,1-6H3,(H,35,41)(H,37,42)
Molecular weight 569.35 Da
AlogP 5.08882
HBond acceptors 9
HBond donors 2
Atoms 85

References

Publications

Cross References

canSARChEMBLBindingDB

Expert Reviews

by SERP
(on 17 May 2016 )
Cellular Use Rating
This probe is a dual inhibitor of EZH1 and EZH2 methyltransferase enzymes (in vitro IC50s are 45 nM and 4.6 nM, respectively), which are the components of Polycomb repressive complex 2. This complex...
by SERP
(on 10 Jun 2016 )
Cellular Use Rating
In Model Organisms
Three days are required for reduction of H3K27me3 in MCF10a cells with IC50 ~135 nM. I recommend using UNC1999 in parallel with its control, UNC2400, and the orthogonal probe, GSK343.
by SERP
(on 19 Apr 2021 )
Cellular Use Rating
In Model Organisms
UNC1999 has utility in cell-based experiments when used in conjunction with UNC2400.
A concentration lower than 1 µM. The cellular IC50 for reduction of H3K27me3 levels is 124 nM. I would suggest 2-3x IC50 to avoid off-targets (e.g., GPCRs) at micromolar concentrations. Suggested to...
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