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. 2008 Apr;13(4):311-20.
doi: 10.1016/j.ccr.2008.02.009.

Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera

Gerlinde Wernig  1 , Michael G Kharas, Rachel Okabe, Sandra A Moore, Dena S Leeman, Dana E Cullen, Maricel Gozo, Elizabeth P McDowell, Ross L Levine, John Doukas, Chi Ching Mak, Glenn Noronha, Michael Martin, Yon D Ko, Benjamin H Lee, Richard M Soll, Ayalew Tefferi, John D Hood, D Gary Gilliland
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"VSports手机版" Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera

Gerlinde Wernig et al. Cancer Cell. 2008 Apr.
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V体育2025版 - Abstract

We report that TG101348, a selective small-molecule inhibitor of JAK2 with an in vitro IC50 of approximately 3 nM, shows therapeutic efficacy in a murine model of myeloproliferative disease induced by the JAK2V617F mutation VSports手机版. In treated animals, there was a statistically significant reduction in hematocrit and leukocyte count, a dose-dependent reduction/elimination of extramedullary hematopoiesis, and, at least in some instances, evidence for attenuation of myelofibrosis. There were no apparent toxicities and no effect on T cell number. In vivo responses were correlated with surrogate endpoints, including reduction/elimination of JAK2V617F disease burden assessed by quantitative genomic PCR, suppression of endogenous erythroid colony formation, and in vivo inhibition of JAK-STAT signal transduction as assessed by flow cytometric measurement of phosphorylated Stat5. .

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