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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
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
MAP3K12
  • Ki:0.5 nM
  • IC50:30 nM
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? Yes

DOI Reference: 10.1021/jm5013984

In Vivo Validations

Mouse
Dose: 1 mg/Kg IV, 5 mg/Kg PO
Route of delivery: Intravenous, Oral
Plasma half life: 0.6. h
Systemic clearance: 56 mL/min/Kg
Bioavailability: 45%
Volume of Distribution at Steady-State: 2.5 L/Kg

DOI Reference: 10.1021/jm5013984

Rat
Dose: 1 mg/Kg IV, 5 mg/Kg PO
Route of delivery: Intravenous, Oral
Plasma half life: 1.8 h
Systemic clearance: 30 mL/min/Kg
Bioavailability: 63%
Volume of Distribution at Steady-State: 3.7 L/Kg

DOI Reference: 10.1021/jm5013984

Dog
Dose: 1 mg/Kg IV, 5 mg/Kg PO
Route of delivery: Intravenous, Oral
Plasma half life: 4 h
Systemic clearance: 41 mL/min/kg
Bioavailability: 32%
Volume of Distribution at Steady-State: 6.5 L/Kg

DOI Reference: 10.1021/jm5013984

Monkey (Cynomolgus)
Dose: 1 mg/Kg IV, 5 mg/Kg PO
Route of delivery: Intravenous, Oral
Plasma half life: 2.4 h
Systemic clearance: 16 mL/min/Kg
Bioavailability: 19%
Volume of Distribution at Steady-State: 3.1 L/Kg

DOI Reference: 10.1021/jm5013984

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 3.515480000000002
HBond acceptors 7
HBond donors 1
Atoms 58

Vendors

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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...
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