Chemical Probes logo
GNE-3511 | Inhibitor of MAP3K12
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
Download

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
MAP3K12
  • Ki:0.5 nM
  • IC50:30 nM
Inhibitor
up to 50 nM

Selectivity

In Vitro Selectivity Assessment

Potency: IC50 - JNK1 129 nM, JNK3 364 nM, MLK1 67.8 nM, MLK2 767 nM, MLK3 602 nM, MKK4 > 5,000 nM, MKK7 > 5,000 nM

Potency Assay Off-Target:
GNE-3511 was assessed against 298 kinases at 0.1 uM in addition to IC50s reported above. Notable off ...

Potency
Cellular
In Vitro

MAP3K12

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? No

In Vivo Validations

Mouse, Rat, Dog, Cyno
Dose: 0.4-1 mg/kg (IV), 5 mg/Kg (PO)
Route of delivery: Intravenous, Oral
Plasma half life: 0.6 (M), 1.8 (R), 4 (D), 2.4 (C) h
Systemic clearance: 56 (M), 30 (R) mL/min/kg
Organ of interest (O): Brain, CSF
Target engagement assay: Indirect: inhibition of protein substrate phosphorylation in retina and substantia nigra

Reference: --

Chemical Information

Molecular Formula C23H26F2N6O
SMILEs N#Cc1ccnc(Nc2cc(C3CCN(C4COC4)CC3)cc(N3CCC(F)(F)C3)n2)c1
InChI InChI=1S/C23H26F2N6O/c24-23(25)4-8-31(15-23)22-11-18(17-2-6-30(7-3-17)19-13-32-14-19)10-21(29-22)28-20-9-16(12-26)1-5-27-20/h1,5,9-11,17,19H,2-4,6-8,13-15H2,(H,27,28,29)
Molecular weight 440.21 Da
AlogP 0.0
HBond acceptors 7
HBond donors 1
Atoms 58

References

Publications

    Cross References

    canSARChEMBLBindingDBPDB

    Vendors

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

    Expert Reviews

    by SERP
    (on 23 Jul 2021 )
    Cellular Use Rating
    In Model Organisms
    This is a relatively promiscuous inhibitor of DLK. As indicated by the published kinome profile, many kinases are >80% inhibited at 100 nM. Care must be exercised when attributing pharmacological observations...
    by SERP
    (on 29 Jul 2021 )
    Cellular Use Rating
    In Model Organisms
    GNE-3511 has been rigorously tested in kinase activity panels and for inhibition of closely related kinases. Biomarkers (p-c-Jun) suggest on-target activity in mouse studies.
    by SERP
    (on 25 Aug 2021 )
    Cellular Use Rating
    In Model Organisms
    While this probe is a good tool for studying DLK inhibition in vitro and in vivo, there is some need to further understand selectivity, especially at higher doses and in a cellular context. Recommended...
    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