Background:

WHI-P154 is an inhibitor of JAK3 with IC50 value of 1.8μM [1].

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].

WHI-P154 shows cytotoxicity against the U373 human glioblastoma cell line in vitro. This antitumor activity can be enhanced by conjugation to EGF. WHI-P154 also shows antitumor activity in a SCID mouse xenograft model of human glioblastoma [2].

参考文献:
[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.