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AZD1480 is a potent JAK2 inhibitor with an IC50 of 0.26 nM. AZD1480 inhibits constitutive and stimulus-induced phosphorylation of JAK2 and STAT-3 in vitro, downstream gene expression, and inhibits cell proliferation. AZD1480 suppresses STAT-3 activation in the glioma-initiating cell population in glioblastoma (GBM) tumors. In vivo, AZD1480 inhibits the growth of subcutaneous tumors and increases survival of mice bearing intracranial GBM tumors by inhibiting STAT-3 activity. Importantly, AZD1480 induces cell death of Kms.11 cells grown in the presence of HS-5 bone marrow (BM)-derived stromal cells and inhibits tumor growth in a Kms.11 xenograft mouse model, accompanied with inhibition of phospho-FGFR3, phospho-JAK2, phospho-STAT3 and Cyclin D2 levels. AZD1480 blocks proliferation, survival, FGFR3 and JAK/STAT3 signaling in myeloma cells cultured alone or cocultured with BM stromal cells, and in vivo, and leads to a decrease in cell proliferation and induction of apoptosis.
Front Immunol. 2022 Feb 7;13:820685.
The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats
AZD1480 purchased from AbMole
| Cell Experiment | |
|---|---|
| Cell lines | Renca or 786-O cells |
| Preparation method | Cell viability assay. Renca or 786-O cells suspended in DMEM medium with 5% FBS were seeded in 96-well plates (5,000 per well) to allow adhesion and then treated with DMSO or AZD1480 for 48 h. Cell viability was determined by MTS assay (Promega, Madison, WI) according to instructions. Absorbance at 490 nm was measured with Mikrotek Laborsysteme (Overath, Germany). Mouse ECs and splenic CD11b+/c− myeloid cells enriched from tumor bearing mice were cultured in 5% FBS 1640 RPMI medium. HUVECs were cultured on collagen 1-coated plates in complete medium (Clonetics). All cells are treated with DMSO and AZD1480 at various doses for 24 h. Cell viability was determined by counting cell number manually. All the experiments were repeated 3 times. |
| Concentrations | 0, 0.1, 0.5, 1.0, 2.5, and 5 μM |
| Incubation time | 48 h |
| Animal Experiment | |
|---|---|
| Animal models | Female BALB/c and athymic nude (NCR-nu/nu) mice (7-8 weeks old) |
| Formulation | water supplemented with 0.5% Hypromellose and 0.1% Tween 80 |
| Dosages | 50 mg/kg once a day or 30 mg/kg twice daily for 21 days |
| Administration | oral gavage |
| Molecular Weight | 348.77 |
| Formula | C14H14ClFN8 |
| CAS Number | 935666-88-9 |
| Solubility (25°C) | DMSO 65 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
[3] Xin H, et al. Cancer Res. Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480.
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