| Description: |
AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1.
IC50 value: 0.26 nM
Target: JAK2
in vitro: AZD1480 demonstrated significant immunoregulatory effects by downregulating T-helper 2 cytokines and chemokines, including IL-13 and thymus- and activation-regulated chemokine, and the surface expression of the immunosuppressive programmed death ligands 1 and 2. Higher concentrations of AZD1480 (5μ) induced G2/M arrest and cell death by inhibiting Aurora kinases . These biological responses to AZD1480 are associated with concomitant inhibition of phosphorylation of JAK2, STAT3 and MAPK signaling proteins. In addition, there is inhibition of expression of STAT3 target genes, particularly Cyclin D2. Examination of a wider variety of myeloma cells (RPMI 8226, OPM-2, NCI-H929, Kms.18, MM1.S and IM-9), as well as primary myeloma cells, showed that AZD1480 has broad efficacy. AZD1480 treatment effectively blocks constitutive and stimulus-induced JAK1, JAK2, and STAT-3 phosphorylation in both human and murine glioma cells, and leads to a decrease in cell proliferation and induction of apoptosis. AZD1480 inhibits STAT3 in tumor-associated myeloid cells, reducing their number and inhibiting tumor metastasis. Myeloid cell-mediated angiogenesis was also diminished by AZD1480, with additional direct inhibition of endothelial cell function in vitro and in vivo.
in vivo: AZD1480 inhibits the STAT3 phosphorylation in an xenograft model of human solid tumors and multiple myeloma. In vivo, AZD1480 inhibits the growth of subcutaneous tumors and increases survival of mice bearing intracranial glioblastoma (GBM) tumors by inhibiting STAT-3 activity, indicating that pharmacologic inhibition of the JAK/STAT-3 pathway by AZD1480 should be considered For study in the treatment of patients with GBM tumors. AZD1480 blocks lung infiltration of myeloid cells and Formation of pulmonary metastases in both mouse syngeneic experimental and spontaneous metastatic models. Furthermore, AZD1480 reduces angiogenesis and metastasis in a human xenograft tumor model.For the detailed information of AZD1480, the solubility of AZD1480 in water, the solubility of AZD1480 in DMSO, the solubility of AZD1480 in PBS buffer, the animal experiment (test) of AZD1480, the cell expriment (test) of AZD1480, the in vivo, in vitro and clinical trial test of AZD1480, the EC50, IC50,and Affinity of AZD1480, Please contact DC Chemicals. |
