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EPZ015666 | EPZ015666 : Inhibitor of PRMT5
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
PRMT5
  • Ki:5 nM
  • IC50:9 nM
Inhibitor
300 nM - 2.5 uM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
No inhibition of 20 Protein methyltransferases at 50 uM (PRMT8, PRMT1, PRMT3, PRMT6, PRMT7, CARM1, D ...

Potency
Cellular
In Vitro

PRMT5

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acsmedchemlett.5b00380

In Vivo Validations

Mouse
Dose: 10 mg/kg, 2 mg/kg (IV)
Route of delivery: Oral
Plasma half life: 1.62 hours (IV)
Systemic clearance: 30.0 mL/min/kg (IV)
Organ of interest (O): xenograft
Target engagement assay: In the SDMA ELISA, Z-138 xenograft tumors collected on day 21 showed dose-dependent changes of >40% and >95% inhibition (>48% and >87% for Maver-1 tumors at day 21; >66% and >95% for Granta-519 tumors at day 18) of the methyl mark achieved at the lowest dose and highest dose, respectively.

DOI Reference: 10.1021/acsmedchemlett.5b00380

Negative Control Compounds

canSAR1582710

Orthogonal Probes def

GSK591
DS-437

Chemical Information

Molecular Formula C20H25N5O3
SMILEs O=C(NC[C@H](O)CN1CCc2ccccc2C1)c1cc(NC2COC2)ncn1
InChI InChI=1S/C20H25N5O3/c26-17(10-25-6-5-14-3-1-2-4-15(14)9-25)8-21-20(27)18-7-19(23-13-22-18)24-16-11-28-12-16/h1-4,7,13,16-17,26H,5-6,8-12H2,(H,21,27)(H,22,23,24)/t17-/m0/s1
Molecular weight 383.20 Da
AlogP 0.4362999999999995
HBond acceptors 8
HBond donors 3
Atoms 53

References

Publications

Cross References

Vendors

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Expert Reviews

by SERP
(on 27 May 2016 )
Cellular Use Rating
In Model Organisms
There is clear evidence showing EPZ015666 inhibits PRMT5 directly in cell-free experiments, including several orthogonal biochemical assays, X-ray crystallography, surface plasmon resonance, SAR, appropriate...
by SERP
(on 30 May 2016 )
Cellular Use Rating
In Model Organisms
EPZ015666 is an excellent potent and selective PRMT5 probe that can be used in cellular systems.
by SERP
(on 21 Jun 2016 )
Cellular Use Rating
In Model Organisms
The reported data for this compound shows potent biochemical and cellular inhibition of the target, and preliminary single dose pharmokinetic (PK) data suggests good coverage above IC90 for 12 hr @...
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