GNE-3511

Inhibitor of MAP3K12

Structure

Information

  • MAP3K12
  • Inhibitor

In Vitro Validations

Uniprot ID: Q12852
Target Class: Protein kinase
Target SubClass: STE
Potency: Ki
Potency Value: 0.5 nM
Potency Assay: DLK Biochemical Assay
PDB ID for probe-target interaction (3D structure): 5CEO
Structure-activity relationship: yes
Target aliases:
Mitogen-activated protein kinase kinase kinase 12, ...

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : 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-target activity was quantified.
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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

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 to DLK inhibitors. I would recommend using other pharmacological interventions (e.g., URMC-099) and genetic interventions to validate studies using GNE-3511.

(last updated: 23 Jul 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

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.

(last updated: 29 Jul 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

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 concentration up to 50nM covers the IC50, but some phenotypes may require more inhibition.

(last updated: 25 Aug 2021 )