Currently, the only potentially curative treatment for MF allogeneic h Hematopoietic stem cells Ethical, traditionally a m Possible option for a small subset of Patients, younger and in good condition, although recent reports suggest its usefulness in patients Bosutinib SKI-606 Well.35 older than 36 alternative therapies are only palliative and without significant influence on survival.37 53 patients die h Frequently failure of the bone marrow with a systemic infection or death hemorrhage.20, 54.55 However, with the discovery of the JAK2V617F mutation JAK2 56 59 emerged as a potential target for the treatment, and several small molecule ATP-competitive JAK2 inhibitors have been developed.60 63 Ruxolitinib is the first and currently the only JAK inhibitor of the U.S. Food and Drug Administration or other Regulierungsbeh rde for the treatment of patients with MF, 64 and the clinical development of several approved JAK inhibitors are underway. Although not as developed as Ruxolitinib, schl Gt the available data on the efficacy of JAK2 inhibitors Similar profiles, CX-4945 Haupt Chlich reduction of enlarged Erten organs and eliminate the symptoms Linked my MF. The differences between them , such a measure of myelosuppression, gastrointestinal and / or neurological side effects. Pr Clinical trials Ruxolitinib Ruxolitinib phosphate oral ATP competitive cyclopentylpropionitrile derived. In pr Clinical studies have in vitro inhibitory activity of t shown against JAK1 and especially JAK2.30 moderate minimum inhibitory activity T was against the non-receptor tyrosine kinase JAK3 and TYK2 disadvantages, as well as the minimal inhibitory activity against several other kinases observed at concentrations approximately 100 times h from than the IC50 for selectivity t against JAK1 JAK1/2. 30 / 2 was determined by measurements of the activity of t in cytokine-stimulated blood STAT assay.30 In a cellular system that contains synthesized lt best justified growth factor independently-dependent Ba/F3 cells expressing JAK2V617F showed dose-Ruxolitinib-dependent reduction mediated JAK2 phosphorylated proteins downstream rts without Ver change their levels in total, 30 suggests that Ruxolitinib exerts its effect by achieve reduced levels of phosphorylated forms. A Hnlicher effect was mononuclear in HEL cell line.30 In these cell lines and in cells from patients with PV Shown antiproliferative and proapoptotic Ruxolitinib Ren observed effects. 30 Similar effects were not observed signs BCRABL or in a cell line that activating one mutation in c KIT.30 Ruxolitinib effects were attenuated cht when cells were treated with primary JAK2V617F acids or immortalized human bone marrow mesenchymal stromal cells, probably due to the activity of cocultured t of mesenchymal stromal paracrine cells.65 Multiple mutations in a cell line Ba / F3 identified JAK2V617F can best be a cause of resistance to Ruxolitinib be experimental in vitro data of systems.66 pr clinical studies in mouse models of JAK1 and JAK2 CONFIRMS as targets for therapy MF. Balb / cM usen Injected with Ba/F3 JAK2V617F Epor significant reductions in size S spleen, tumor burden and circulating cytokines, had usen as treated Ruxolitinib treated disadvantages treatment.