生物活性

• 靶点	JAK2 IC50:0.26nM

• 描述The signal transducer and activator of transcription (STAT) activation by cytokines is mediated through the Janus family kinases (Jak), which include four family members, Jak1, Jak2, Jak3, and Tyk2. JAK2 is a Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. JAK2 mediates essential signaling events in both innate and adaptive immunity. Following ligand-binding to cell surface receptors, JAK2 phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. AZD1480 is a potent ATP competitive inhibitor of JAK2 kinase, with an inhibition constant (Ki) of 0.26nM. The enzyme IC₅₀ of AZD1480 against JAK2, JAK1 and JAK3 were <0.4nM, 1.3nM and 3.9nM, respectively, at K_m ATP^[3]. In TEL-JAK2 cells, AZD1480 concentration-dependently inhibited the phosphorylation of Stat5 ranging from 0.03μM to 1μM, with an IC₅₀ of 46nM. Little or no inhibition of Stat5 phosphorylation was observed in the TEL-Jak3, TEL-Jak1, or TEL-Tyk2 cells at below 1μM AZD1480^[3]. At concentrations ranging from 0.5μM to 3μM, AZD1480 blocked cell proliferation and induces apoptosis of myeloma cell lines^[4]. In animal experiments, AZD1480 decreased tumor growth in Renca, Kms.11, TC32, Rh18 or patient derived Glioblastoma xenografts. In different experiments, AZD1480 was orally dosed 50mg/kg once a day or 30mg/kg, twice a day^[5].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  4C8	1 µM	Function Assay	0-16 h	inhibits constitutive STAT-3 and JAK2 activation	22027691
  4C8	1/10 µM	Growth Inhibition Assay	24/48/72 h	inhibits cell proliferation at a concentration of 10 µM	22027691
  686LN	-	Growth Inhibition Assay	72 h	EC50=2.05 ± 1.33 μM	25810010

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• 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
  NCT00910728	Primary Myelofibrosis (PMF) ... more >> Post-Polycythaemia Vera Essential Thrombocythaemia Myelofibrosis Collapse <<	Phase 1	Completed	-	United States, New York ... more >> Research Site New York, New York, United States United States, Texas Research Site Houston, Texas, United States France Research Site Villejuif Cedex, France Collapse <<
  NCT01112397	Solid Malignancies	Phase 1	Terminated(Decision to stop de... more >>velopment of AZD1480) Collapse <<	-	United States, Colorado ... more >> Research Site Aurora, Colorado, United States United States, Michigan Research Site Detroit, Michigan, United States United States, Pennsylvania Research Site Philadelphia, Pennsylvania, United States Collapse <<
  NCT00910728	-	-	Completed	-	-

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