Background:

WHI-P97 is a rationally designed potent inhibitor of JAK-3.IC50 value:Target: JAK3Treatment of mast cells with WHI-P97 inhibited the translocation of 5-lipoxygenase (5-LO) from the nucleoplasm to the nuclear membrane and consequently 5-LO-dependent leukotriene (LT) synthesis after IgE receptor/FcepsilonRI crosslinking by >90% at low micromolar concentrations. WHI-P97 did not directly inhibit the enzymatic activity of 5-LO, but prevented its translocation to the nuclear membrane without affecting the requisite calcium signal. WHI-P97 was very well tolerated in mice, with no signs of toxicity at dose levels ranging from 5 microg/kg to 50 mg/kg, and LD(10) was not reached at a 50 mg/kg dose level when administered as a single i. p. or i.v. bolus dose.

参考文献:
[1]. Ji KA, Yang MS, Jou I, Shong MH, Joe EH.Thrombin induces expression of cytokine-induced SH2 protein (CIS) in rat brain astrocytes: involvement of phospholipase A2, cyclooxygenase, and lipoxygenase.Glia. 2004 Nov 1;48(2):102-11.
[2]. Wong WS, Leong KP.Tyrosine kinase inhibitors: a new approach for asthma.Biochim Biophys Acta. 2004 Mar 11;1697(1-2):53-69.
[3]. Uckun FM, Sudbeck EA, Mao C, Ghosh S, Liu XP, Vassilev AO, Navara CS, Narla RK.Structure-based design of novel anticancer agents.Curr Cancer Drug Targets. 2001 May;1(1):59-71.
[4]. Sudbeck EA, Liu XP, Narla RK, Mahajan S, Ghosh S, Mao C, Uckun FM.Structure-based design of specific inhibitors of Janus kinase 3 as apoptosis-inducing antileukemic agents.Clin Cancer Res. 1999 Jun;5(6):1569-82.