Chemical Probes logo
EPZ004777 | EPZ004777 : SAM competitive inhibitor of DOT1L
RATINGS:
Cellular Use: (4 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
Download

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
DOT1L
  • IC50:0.4 nM
  • IC50:700 nM
SAM competitive
1 uM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
EPZ004777 is >1,000-fold selective for DOT1L over other PMTs tested (CARM1, EHMT2, EZH1, EZH2, PRMT1 ...
Selectivity Assessment Description:
Not available
In Cell Selectivity Assessment
Potency Assay Off-Target:
PRMT5 (H4R3), PRDMs ((H3K9) and SMYDs (H3K4) protein substrates were not impacted in cells.
Selectivity Assessment Description:
Not available

Potency
Cellular
In Vitro

DOT1L

Mode of Action: SAM competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1016/j.ccr.2011.06.009

In Vivo Validations

Mouse
Dose: 50 mg/mL continuous infusion
Route of delivery: Subcutaneous
Organ of interest (O): MV4-11 xenograft
Target engagement assay: Indirect, decrease in substrate methylation in the tumor. Authors noted that EPZ004777 had a poor PK profile, which necessitated delivery by continuous infusion.

DOI Reference: 10.1016/j.ccr.2011.06.009

Orthogonal Probes def

SGC0946

Chemical Information

Molecular Formula C28H41N7O4
SMILEs CC(C)N(CCCNC(=O)Nc1ccc(C(C)(C)C)cc1)C[C@H]1O[C@@H](n2ccc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChI InChI=1S/C28H41N7O4/c1-17(2)34(13-6-12-30-27(38)33-19-9-7-18(8-10-19)28(3,4)5)15-21-22(36)23(37)26(39-21)35-14-11-20-24(29)31-16-32-25(20)35/h7-11,14,16-17,21-23,26,36-37H,6,12-13,15H2,1-5H3,(H2,29,31,32)(H2,30,33,38)/t21-,22-,23-,26-/m1/s1
Molecular weight 539.32 Da
AlogP 2.8524
HBond acceptors 11
HBond donors 6
Atoms 80

Vendors

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

Expert Reviews

by SERP
(on 21 Jan 2017 )
Cellular Use Rating
This DOT1L inhibitor was the first potent DOT1L ligand disclosed (by Epizyme) in 2011. EPZ004777 is an extremely potent and selective DOT1L inhibitor, making this an ideal probe for cellular use. The...
by SERP
(on 28 Mar 2017 )
Cellular Use Rating
EPZ004777 is an excellent probe for cellular experiments. It specifically affected the MLL-translocated leukemia lines that are dependent on DOT1L recruitment and enzymatic function. Due to the PK limitationsof...
by SERP
(on 27 Apr 2017 )
Cellular Use Rating
In Model Organisms
...
by SERP
(on 27 Apr 2017 )
Cellular Use Rating
In Model Organisms
EPZ-5676, a derivative with a better pharmacokinetic profile than this probe, would be the better choice for a DOT1L chemical probe. EPZ-5676 is available commercially and is listed in the Portal. There...
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