FM-381

Covalent Inhibitor of JAK3

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 ratings)

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Information

JAK3

Covalent Inhibitor

100 nM - 1 uM

DOI - 10.1016/j.chembiol.2016.10.008

Probe Availability:

In Vitro Validations

Uniprot ID: P52333

Target Class: Kinase

Target SubClass: TK

Potency: IC50(app)

Potency Value: 0.154 nM

Potency Assay: Radiometric assay

PDB ID for probe-target interaction (3D structure): 5LWM

Structure-activity relationship: Yes, see Cell Chem Biol paper

Target aliases:

Tyrosine-protein kinase JAK3, JAK3, JAK3_HUMAN, L- ...

DOI Reference: 10.1016/j.chembiol.2016.10.008

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency end-point : IC50(app) JAK1: 52 nM, JAK2: 346 nM, TYK2: 459 nM, BTK >5 uM, ITK: 1.8 uM, EGFR >5 uM

Potency assay (off target): In addition to assays assessing acivity against closely related kinases and those with a Cys comparable to Cys909 found in the gatekeeper position on JAK3 (above), FM-381 was assayed in a panel of 410 protein kinases (ProQinase), with no significant activity detected at 100 nM and weak activity detected at 500 nM.

Probe Selectivity in Vitro:

FM-381 was largely inactive against a panel of bromodomain proteins. The most potent activity was: TAF1 IC50=500 nM.

Potency assay, off target (cells): In human CD4+ T cells, FM-381 did not inhibit IL-6-stimulated STAT3 phosphorylation at 1 uM.

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SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 27 Apr 2017 )

SERP Ratings

In Cell Rating

SERP Comments:

This is a highly selective probe for JAK3 compared with close family members (and the wider Kinome) with parallel cellular selectivity disclosed.

(last updated: 5 May 2017 )

SERP Ratings

In Cell Rating

(last updated: 1 Jun 2017 )