生物活性

As a member of the tyrphostin family, AG-490 is reported to have inhibitory activity against many kinases. It can inhibit the hyperactive JAK2 in B cell precursors of ALL patients, inhibit cytokine-induced activation of JAK2 in eosinophils and suppresses the activation of STAT3 in mycosis fungoides-derived T cells. AG-490 is also found to target JAK3 and its downstream STAT and MAPK signaling pathways. In the IL-2-dependent T cell line, D10, AG-490 suppresses IL-2-induced cell proliferation with IC50 value of 25μM without affecting IL-2R chain expression. It also inhibits IL-2-modulated phosphorylation of STAT5a and STAT5b with IC50 value of 50μM-70μM. Moreover, AG-490 reduces IL-2-induced DNA binding by 78%, 65% and 65% for STAT5a/5b, STAT1 and STAT3, respectively. All these show that AG-490 may provide a beneficial therapeutic by suppressing immunopathological states.

体外研究

体内研究

1% DMSO+30% polyethylene glycol+1% Tween 80

激酶实验

细胞实验

~ 50 μM

动物实验

每天0.85 mg + 0.5 mg 持续输液泵输液加之以每天腹腔注射

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

[1] Gazit A, et al. J Med Chem, 1991, 34(6), 1896-1907.
[2] Potier, et al., Protein tyrosine kinase inhibitors reduce high-voltage activating calcium currents in CA1 pyramidal neurones from rat hippocampal slices. Brain Res. 816, 587-597, (1999)
[3] Eriksen, K.W., et al., Constitutive STAT3-activation in Sezary syndrome: tyrphostin AG490 inhibits STAT3-activation, interleukin-2 receptor expression and growth of leukemic Sezary cells. Leukemia 15, 787-793, (2001)

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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