NIK-SMI1

Inhibitor of MAP3K14

Structure

Information

Protein target names: MAP3K14

Mechanism of action: Inhibitor

Recommended in-cell concentration:
100 nM

Reviewer recommended in-cell concentration: 150-400 nM

In Vitro Validations

Uniprot ID: Q99558
Target Class: Kinase
Target SubClass: STE
Potency: Ki
Potency Value: 0.23 ± 0.17 nM
Potency Assay: NIK Ki biochemical assay
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: yes
Target aliases:
Mitogen-activated protein kinase kinase kinase 14, ...

DOI Reference: 10.1021/acs.jmedchem.8b00678

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

Comments:

NIK SMI1:

  • Is a highly potent and selective NF-κB-inducing kinase (NIK) inhibitor with Ki of 0.23 nM for NIK-catalyzed hydrolysis of ATP to ADP.
  • Inhibits expression of NF-κB response element regulated firefly luciferase reporter gene in HEK293 cells at an IC50 of 34 nM.
  • has a favorable pharmacokinetic profile across species.  
  • Inhibits BAFF-induced B cell survival in vitro (close to phenotype assay) at an IC50 of 373 nM. 
  • Inhibits BAFF signalling and reduces splenic marginal zone B cells in mice at doses from 60-200 mg/kg.

(last updated: 8 Dec 2020 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

The primary references provide strong support for on target NIK (MAP3K14) potency, efficacy and selectivity within the kinome for NIK SM1. In functional assays ~1 uM in cells and 200 mg/kg BID orally in C57BL/6 mice are recommended based on the data in the provided references. Selectivity profiling outside the kinome for safety pharmacology is not available and this unknown should modulate interpretation of in vivo results if readouts differ from the systems investigated in the references.

(last updated: 2 Mar 2021 )