TG-101348又称为Fedratinib、SAR 302503，是一种ATP竞争性的、高选择性JAK2抑制剂（IC₅₀=3 nM），比作用于JAK3的IC₅₀值高300倍。TG-101348抑制JAK2V617F突变的人红细胞白血病细胞系增殖，并抑制一种表达人JAK2V617F（Ba/F3 JAK2V617F）的鼠前B细胞系增殖，IC₅₀约为300 nM。与Erlotinib联合使用时，TG-101348显著增强Erlotinib的细胞毒性作用，刺激Erlotinib诱导的细胞凋亡，并下调Erlotinib耐受的NSCLC细胞中EGFR、p-EGFR、p-STAT3、Bcl-xL和survivin的表达。

TG-101348具体良好耐受性，目前已用于临床Phase 2研究阶段。

参考文献

[1] Wernig G, et al. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell. 13(4): 311-320 (2008).

[2] Geron I, et al. Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors. Cancer Cell. 2008 13(4): 321-330 (2008).

[3] Lasho T, et al. Inhibition of JAK-STAT signaling by TG101348: a novel mechanism for inhibition of KITD816V-dependent growth in mast cell leukemia cells. Leukemia. 24(7): 1378-1380 (2010).

[4] Zhang FQ, et al. JAK2 inhibitor TG101348 overcomes erlotinib-resistance in non-small cell lung carcinoma cells with mutated EGF receptor. Oncotarget 6(16): 14329-14343 (2015).

冰袋运输。粉末直接保存于-20 ºC，有效期2年。溶于DMSO。建议分装后-20ºC避光保存，避免反复冻存，至少可存放6个月。