JAK3 Inhibitor

Description

WHI-P154 is a quinazoline derivative that exhibits immunosuppressive effects by selectively inhibiting JAK3 (IC₅₀ = 1.8 μM versus IC₅₀s > 10 μM for JAK1 and JAK2). It has been reported to inhibit additional kinases including EGFR (IC₅₀ = 4 nM) and VEGFR as well as the non-receptor tyrosine kinases, Abl, Lck, and Src. WHI-P154 is cytotoxic to human glioblastoma cells (IC₅₀ = 813 nM) and has been used to induce the differentiation of neuronal precursor cells.

The Uses of JAK3 Inhibitor

WHI-P154 is a potent JAK3 inhibitor with IC50 of 1.8 μM and also inhibits EGFR with IC50 of 4 nM.

The Uses of JAK3 Inhibitor

WHI-P154 can act as antileukemic agent with apoptosis inducing activity.

What are the applications of Application

WHI-P 154 is a JAK3 inhibitor which inhibits other common kinases

Biochem/physiol Actions

WHI-P154 is a specific inhibitor of JAK3 (IC50 = 1.8 μM) with no inhibitory activity against JAK1 or JAK2. WHI-P154 enhances myogenic differentiation of C2C12 mouse myoblast cells, and induces differentiation of neural progenitor cells. The compound WHI-P154 dose dependently inhibits expression of iNOS and NO production in LPS-challenged macrophages.

in vitro

kinase assays show that whi-p154 is not a specific inhibitor. besides jak3, it also inhibits many other kinases, including egfr, abl, lck, src and vegfr. whi-p154 inhibits egfr with ic50 value of 4nm. the specificity of whi-p154 has not been shown in cell-based assays either [1].

Storage

Store at RT

References

[1] changelian ps, moshinsky d, kuhn cf, flanagan me, munchhof mj, harris tm, whipple da, doty jl, sun j, kent cr, magnuson ks, perregaux dg, sawyer ps, kudlacz em. the specificity of jak3 kinase inhibitors. blood. 2008 feb 15;111(4):2155-7.
[2] narla rk, liu xp, myers de, uckun fm. 4-(3'-bromo-4'hydroxylphenyl)-amino-6,7-dimethoxyquinazoline: a novel quinazoline derivative with potent cytotoxic activity against human glioblastoma cells. clin cancer res. 1998 jun;4(6):1405-14.