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Pevonedistat | Pevonedistat : Inhibitor of UBA3
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
UBA3
  • IC50:4.7 nM
  • IC50:<100 nM
Inhibitor
0.3 uM

Selectivity

In Vitro Selectivity Assessment

Potency: IC50 - UAE: 1.5 uM, SAE: 8.2 uM, UBA6: 1.8 uM, ATG7 >10 uM

Potency Assay Off-Target:
Purified enzyme assays monitoring the formation of E2-UBL thioester reaction products.
Selectivity Assessment Description:
Pevonedistat had no effect on RNA synthetases in assays monitoring 35S-Met incorporation into new ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
In HCT-116 cells, pevonedistat had no effect on non-CRL substrates (e.g., GADD34, securin, cyclin B, ...

Potency
Cellular
In Vitro

UBA3

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1038/nature07884

In Vivo Validations

Female athymic NCR mice
Dose: 10-60 mg/kg
Route of delivery: Subcutaneous
Organ of interest (O): HCT-116 xenografts, bone marrow
Target engagement assay: In both xenografts and bone marrow, pevonedistat dose-dependently decreased NEDD8-cullin levels.

DOI Reference: 10.1038/nature07884

Orthogonal Probes def

ABPA3

Chemical Information

Molecular Formula C21H25N5O4S
SMILEs NS(=O)(=O)OC[C@@H]1C[C@@H](n2ccc3c(N[C@H]4CCc5ccccc54)ncnc32)C[C@@H]1O
InChI InChI=1S/C21H25N5O4S/c22-31(28,29)30-11-14-9-15(10-19(14)27)26-8-7-17-20(23-12-24-21(17)26)25-18-6-5-13-3-1-2-4-16(13)18/h1-4,7-8,12,14-15,18-19,27H,5-6,9-11H2,(H2,22,28,29)(H,23,24,25)/t14-,15+,18-,19-/m0/s1
Molecular weight 443.16 Da
AlogP 0.0
HBond acceptors 9
HBond donors 4
Atoms 56
PAINS * Yes

* This is an automated alert only, and may not necessarily indicate an issue with this probe. ( Learn more about PAINS )

Vendors

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Expert Reviews

by SERP
(on 28 Jun 2017 )
Cellular Use Rating
In Model Organisms
MLN4924 is a covalent and cell-permeable inhibitor of NAE. Shows strong selectivity over closely related proteins in biochemical assays as well as reasonable potency in cellular neddylation assays (dose...
by SERP
(on 7 Jul 2017 )
Cellular Use Rating
If possible, use Pevonedistat in parallel with a positive or negative control compound.
by SERP
(on 7 Jul 2017 )
Cellular Use Rating
In Model Organisms
MLN4924 is a potent inhibitor of NEDD8-activating enzyme which is selective for other activating enzymes in the Ubiquitin family of ligases. This probe is active in cellular assays in which Ubc12-NEDD8...
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