JNK-IN-8

Covalent Inhibitor of MAPK8, MAPK9, MAPK10

Structure

Information

  • MAPK8
  • MAPK9
  • MAPK10
  • Covalent Inhibitor

In Vitro Validations

Uniprot ID: P45983
Target Class: Kinase
Target SubClass: CMGC
Potency: IC 50
Potency Value: 14.7 nM
Potency Assay: In vitro kinase assay
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Mitogen-activated protein kinase 8, SAPK1C, SAPK1, ...

DOI Reference: 10.1016/j.chembiol.2011.11.010

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): 442 kinases were tested in DiscoveRx panel, and 121 kinases were tested in radiometric assays. With cellular data, JNK-IN-8 did not inhibit any off-target kinases with an IC50< 1 uM.
Probe Selectivity in Vitro:
442 kinases were tested in DiscoveRx panel, and 121 kinases were tested in radiometric assays. With cellular data, JNK-IN-8 did not inhibit any off-target kinases with an IC50< 1 uM.
Potency assay, off target (cells): 200 kinases were assays in A375 cells using KiNativ. With in vitro data, JNK-IN-8 did not inhibit any off-target kinase with an IC50< 1 uM.
Probe Selectivity in Cell:
200 kinases were assays in A375 cells using KiNativ. With in vitro data, JNK-IN-8 did not inhibit any off-target kinase with an IC50< 1 uM.
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SERP ratings and comments


SERP Ratings

In Cell Rating

SERP Comments:

JNK-IN-8 is a covalent and highly selective JNK1/2/3 inhibitor with well validated activity in cells. The JNK family of kinases (also known as the stress-activated protein kinases, SAPK) play a significant role in the cellular response to cytokines and environmental stress. The literature surrounding these targets is vast, with JNK inhibition possibly being of utility in cancer, diabetes, Alzheimer’s disease and endometriosis. Unfortunately, the literature is also sometimes confusing and contradictory. Good small molecule tools like JNK-IN-8 are essential to the study of these important targets. JNK-IN-8 should prove a useful tool when used alongside other validated JNK inhibitors including bentamapimod, XG-102 and tanzisertib.     

(last updated: 20 Jun 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

This is a potent JNK1/2/3 inhibitor with some off target activity (MNK2, FMS at 200-500 nM).

(last updated: 21 Jun 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

JNK-IN-8 is an imatinib-derived pan-JNK inhibitor (biochemical IC50 values: 4.7 nM (JNK1), 18.7 nM (JNK2), 1 nM (JNK3)). Its covalent-irreversible binding mode is reasonable validated by X-ray structures and protein mass spectroscopy of close analogues. While showing high potency in biochemical assays on the isolated JNKs, the compound suffers from a surprisingly low inhibitory activity in a cellular environment (IC50 300-500 nM). Kinome-wide screening revealed several highly potent off target hits, but most of them could not be validated in subsequent IC50 or Kd determinations (e.g., FMS and MNK2, ~200-300 nM). JNK-IN-8 may serve as a chemical probe in cells to investigate unselective JNK inhibition. It should be used with caution along with another positive control compound.

(last updated: 27 May 2017 )