JAK3i
Irreversible inhibitor of JAK3
Structure
In Cells
In Model Organisms
SERP ratings and comments
SERP Ratings
SERP Comments:
Broad kinase selectivity of this probe needs to be determined before it can be recommended for use. Potency data for all kinases with the structurally equivalent cysteine should be reported.
(last updated: 9 Sept 2016 )
SERP Ratings
SERP Comments:
(last updated: 7 Apr 2017 )
SERP Comments:
JAK3i is an irreversible probe molecule with good selectivity over closely related kinases. However, the paper lacks broader kinase selectivity data and this should be generated, especially for kinases with a cysteine in a structurally similar position, prior to use in cells.
(last updated: 7 Apr 2017 )
SERP Ratings
SERP Comments:
Importantly, the in vivo effects of this probe on IL-2-driven proliferation were shown to be JAK3-dependent by using a mutant JAK3 (C905S JAK3), which exhibits similar activity to wild-type JAK3 but is not inhibited by their probe.
(last updated: 10 Apr 2017 )
SERP Comments:
It would be helpful to see a more detailed selectivity assessment, but JAK3i appears reasonably selective with ~50-fold selectivity over BTK. The use of a C905S mutant to rescue demonstrates a clear JAK3-dependent effect for the compound. I would prefer further characterization of the compound to feel comfortable interpreting experimental results in any context that lacks a C905S mutant control. Additional PK/PD data would be valuable to guide use of the compound in vivo.
(last updated: 11 Apr 2017 )