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EPZ-5676 | Inhibitor of DOT1L
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
DOT1L
  • Ki:0.08 nM
  • IC50:3 nM
Inhibitor
Up to 100 nM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
Minimal off-target activity against 16 protein methyltransferases up to 10 uM EPZ5676. At 10 uM, PRM ...

Potency
Cellular
In Vitro

DOT1L

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? No

DOI Reference: 10.1182/blood-2013-04-497644

In Vivo Validations

Mouse, Rat
Dose: 20 mg/kg (mice), 1 mg/kg (rat)
Route of delivery: Intraperitoneal, Intravenous
Plasma half life: 5.22 h (mouse), 3.73 h (rat)
Systemic clearance: 4.07 L/h/kg (rat)
Organ of interest (O): xenograft tumor
Target engagement assay: Indirect, protein substrate methylation assay with inhibitory activity detected in the tumor and surrogate tissues, bone marrow and PBMCs

DOI Reference: 10.1182/blood-2013-04-497644

Orthogonal Probes def

SGC0946
EPZ004777

Chemical Information

Molecular Formula C30H42N8O3
SMILEs CC(C)N(C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O)C1CC(CCc2nc3cc(C(C)(C)C)ccc3[nH]2)C1
InChI InChI=1S/C30H42N8O3/c1-16(2)37(13-22-25(39)26(40)29(41-22)38-15-34-24-27(31)32-14-33-28(24)38)19-10-17(11-19)6-9-23-35-20-8-7-18(30(3,4)5)12-21(20)36-23/h7-8,12,14-17,19,22,25-26,29,39-40H,6,9-11,13H2,1-5H3,(H,35,36)(H2,31,32,33)/t17?,19?,22-,25-,26-,29-/m1/s1
Molecular weight 562.34 Da
AlogP 3.3233
HBond acceptors 11
HBond donors 5
Atoms 83

References

Publications

Cross References

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Expert Reviews

by SERP
(on 17 Jun 2016 )
Cellular Use Rating
In Model Organisms
EPZ-5676 continuous IV infusion for 21 days in a xenograft model of MLL-rearranged leukemia leads to dose-dependent anti-tumor activity. At the highest dose of 70.5 mg/kg/day, complete tumor regression...
by SERP
(on 24 Jun 2016 )
Cellular Use Rating
In Model Organisms
EPZ-5676 (pinometostat) is a first-in-class inhibitor of DOT1L activity. EPZ-5676 is a potent and selective inhibitor of DOT1L with activity in both cellular and rodent MLL-models. Nonclinical in vivo...
by SERP
(on 2 Jun 2017 )
Cellular Use Rating
In Model Organisms
( The reviewer did not leave any comments )
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