@article{08484d12c33a42ad9b38cd6af7658d4f,
title = "Efficacy of TG101348, a Selective JAK2 Inhibitor, in Treatment of a Murine Model of JAK2V617F-Induced Polycythemia Vera",
abstract = "We report that TG101348, a selective small-molecule inhibitor of JAK2 with an in vitro IC50 of ∼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.",
keywords = "CELLCYCLE, CHEMBIO",
author = "Gerlinde Wernig and Kharas, {Michael G.} and Rachel Okabe and Moore, {Sandra A.} and Leeman, {Dena S.} and Cullen, {Dana E.} and Maricel Gozo and McDowell, {Elizabeth P.} and Levine, {Ross L.} and John Doukas and Mak, {Chi Ching} and Glenn Noronha and Michael Martin and Ko, {Yon D.} and Lee, {Benjamin H.} and Soll, {Richard M.} and Ayalew Tefferi and Hood, {John D.} and Gilliland, {D. Gary}",
note = "Funding Information: This work was supported by the Howard Hughes Medical Institute (D.G.G.), the National Institutes of Health grants CA66996 (to D.G.G.) and CA105423 (to D.G.G.), grants from the Doris Duke Charitable Foundation (to D.G.G.), the Leukemia and Lymphoma Society, and the MPD Foundation (to D.G.G.). D.G.G. is a Doris Duke Charitable Foundation Distinguished Clinical Scientist. G.W. is a recipient of a Special Fellow Award from the Leukemia and Lymphoma Society. Funding was also provided by Targegen for the authors at Targegen. J.D., C.C.M., G.N., M.M., R.M.S., and J.D.H. are employees of Targegen that generated TG101348 for human clinical trials. All other authors declare that they have no competing financial interests. ",
year = "2008",
month = apr,
day = "8",
doi = "10.1016/j.ccr.2008.02.009",
language = "English (US)",
volume = "13",
pages = "311--320",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}