2. Academic Validation
  3. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera

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

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

Affiliation

  • 1 Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
PMID: 18394554 DOI: 10.1016/j.ccr.2008.02.009
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. 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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