生物活性

• 靶点

  Bromodomain 4 IC50:340nM

  JAK2 IC50:3nM

• 描述Fedratinib is a selective JAK2 inhibitor with IC50 values of 3nM, 3nM, 15nM and 48nM for JAK2, JAK2 V617F, Flt3 and Ret, respectively. Fedratinib inhibited proliferation of a human erythroblast leukemia (HEL) cell line that harbors the JAK2V617F mutation, as well as a murine pro-B cell line expressing human JAK2V617F (Ba/F3 JAK2V617F), with an IC50 value of approximately 300nM for either line. Exposure of these cells to Fedratinib reduced STAT5 phosphorylation at concentrations that parallel the concentrations required to inhibit cell proliferation. Also it induced apoptosis in both HEL and Ba/F3 JAK2V617F cells in a dose-dependent manner. It showed therapeutic efficacy in a murine model of myeloproliferative disease induced by the JAK2V617F mutation. It triggered 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^[2].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  Ba/F3 JAK2V617F	-	Growth Inhibition Assay	-	IC50=270 nM	18394554
  Bcr-abl	-	Growth Inhibition Assay	-	IC50=2.7 (2.2–3.3) μM	24251790
  Caco-2	0-120 μM	Function Assay	7 min	inhibits thiamine uptake with an IC50 of 2.1 µM	25063672

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• 动物研究
  剂量	Mice: 1 g/kg[2] (p.o.), 30 mg/kg - 200 mg/kg[1] (p.o.) Rat: 2 mg/kg[3] (i.v.)
  给药途径	p.o., i.v.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01437787	Hematopoietic Neoplasm	Phase 3	Completed	-	-
  NCT01585623	Solid Tumor	Phase 1	Completed	-	United States, Georgia ... more >> Investigational Site Number 840004 Augusta, Georgia, United States, 30912 United States, Michigan Investigational Site Number 840001 Detroit, Michigan, United States, 48201 United States, Pennsylvania Investigational Site Number 840002 Philadelphia, Pennsylvania, United States, 19111 Collapse <<
  NCT01836705	Neoplasm Malignant	Phase 1	Completed	-	United States, California ... more >> Investigational Site Number 840003 Los Angeles, California, United States, 90048 United States, Georgia Investigational Site Number 840007 Augusta, Georgia, United States, 30912 United States, Michigan Investigational Site Number 840002 Detroit, Michigan, United States, 48201 United States, Missouri Investigational Site Number 840001 St Louis, Missouri, United States, 63110 United States, Ohio Investigational Site Number 840004 Cincinnati, Ohio, United States, 45267-0542 United States, Pennsylvania Investigational Site Number 840005 Philadelphia, Pennsylvania, United States, 19111 United States, Texas Investigational Site Number 840006 San Antonio, Texas, United States, 78229 Investigational Site Number 840008 San Antonio, Texas, United States, 78229 Belgium Investigational Site Number 056001 Bruxelles, Belgium, 1200 Investigational Site Number 056002 Gent, Belgium, 9000 Collapse <<

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• 参考文献

• [1] Wernig G, Kharas MG, et al. 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.

  [2] Wernig G, Kharas MG, Okabe R, Moore SA, Leeman DS, Cullen DE, Gozo M, McDowell EP, Levine RL, Doukas J, Mak CC, Noronha G, Martin M, Ko YD, Lee BH, Soll RM, Tefferi A, Hood JD, Gilliland DG. 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. PMID: 18394554.