1. Epigenetics
    Stem Cell/Wnt
    JAK/STAT Signaling
  2. JAK

AZD-1480 (Synonyms: AZD1480; AZD 1480)

Cat. No.: HY-10193 Purity: 99.37%
Data Sheet SDS Handling Instructions

AZD-1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM, selectively against JAK3 and Tyk2, and to a smaller extent against JAK1.

For research use only. We do not sell to patients.
AZD-1480 Chemical Structure

AZD-1480 Chemical Structure

CAS No. : 935666-88-9

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10 mM * 1 mL in DMSO $55 In-stock
5 mg $50 In-stock
10 mg $80 In-stock
50 mg $200 In-stock
100 mg $360 In-stock
200 mg $650 In-stock
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    AZD-1480 purchased from MCE. Usage Cited in: Leukemia. 2012 Oct;26(10):2233-44.

    Drug combination effect on phosphorylation of AKT. Expression of phospho-AKT and total AKT in MOLM13 cells treated for 15 minutes with DMSO vehicle, PKC412 (2.5 nM), Dasatinib (165 nM), or a combination of both. Protein lysates are prepared from MOLM13 cells, and are analyzed via immunoblotting with antibodies to phospho-AKT and total AKT.

    AZD-1480 purchased from MCE. Usage Cited in: Leukemia. 2012 Oct;26(10):2233-44.

    SCM stimulation of phospho-STAT5 and drug combination effect on phosphorylation of phospho-STAT5. Expression of phospho-STAT5 and total STAT5 in MOLM13 cells treated for 1.5 h with DMSO vehicle, PKC412 (5 nM), KIN40 (82.5 nM) or a combination of both. Results shown are representative of two independent experiments in which similar results are observed.

    AZD-1480 purchased from MCE. Usage Cited in: Neuro Oncol. 2017 Jan;19(1):22-30.

    AZD1480 and RXDX-101 decrease pSTAT3 levels in a dose- and time-dependent manner. (A) Ink4a−/−/Arf−/−/NTRK2-TEL astrocytes are treated with different concentrations of AZD1480 (upper panel) or RXDX-101 (lower panel) for 1 h. (B) Cells are treated with 0.5 μM AZD1480 (upper panel) or 0.05 μM RXDX-101 (lower panel) for the indicated times. Western blot analyses are then performed with the indicated antibodies. Band intensities of pSTAT3 are quantified and normalized relati

    AZD-1480 purchased from MCE. Usage Cited in: Biomed Pharmacother. 2017 Sep 25;95:1799-1808.

    The expression of Bcl-2, Bax, pro-Caspase-3 and cleaved-Caspase-3 by western blotting. Representative western blots showing the effects of apigenin and AZD1480 on Bax, Bcl-2, pro-Caspase-3 and cleaved-Caspase-3 expression levels.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AZD-1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM, selectively against JAK3 and Tyk2, and to a smaller extent against JAK1.

    IC50 & Target

    IC50: 0.26 nM (JAK2)

    In Vitro

    AZD1480 (5μM) induces G2/M arrest and cell death by inhibiting Aurora kinases[1]. AZD1480 is a potent JAK2 inhibitor that can suppress growth, survival, as well as FGFR3 and STAT3 signaling and downstream targets including Cyclin D2 in human multiple myeloma cells. At low micromolar concentrations, AZD1480 blocks cell proliferation and induces apoptosis of myeloma cell lines[2]. AZD1480 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[3]. AZD1480 is a potent, competitive small-molecule inhibitor of JAK1/2 kinase, and that it is capable of inhibiting STAT3 phosphorylation and tumor growth in a STAT3-dependent manner. AZD1480 inhibits tumor angiogenesis and metastasis in part by affecting the tumor microenvironment[4].

    In Vivo

    AZD1480 inhibits the STAT3 phosphorylation in an xenograft model of human solid tumors and multiple myeloma[1]. 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[3]. 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[4]. AZD1480 suppresses the growth of human solid tumor xenografts harboring persistent Stat3 activity[5].

    Clinical Trial
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    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.8672 mL 14.3361 mL 28.6722 mL
    5 mM 0.5734 mL 2.8672 mL 5.7344 mL
    10 mM 0.2867 mL 1.4336 mL 2.8672 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [5]

    Inhibition studies of AZD1480 are performed using recombinant Jak1, Jak2, or Jak3 under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween-20, 50 mM/mL BSA, and 10 mM MgCl2. Jak3 enzyme is expressed as N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes are assayed in the presence of AZD1480 (10 point dose response, in triplicate, from 8.3 μM to 0.3 nM in half-log dilution steps) using 1.5 μM peptide substrate (Jak1: FITC-C6-KKHTDDGYMPMSPGVA-NH2, Jak2 and Jak3: FAM-SRCtide) and screened under their respective ATP Km (Jak1: 55 μM, Jak2: 15 μM, Jak3: 3 μM) and approximated physiological ATP concentration of 5 mM. Phosphorylated and unphosphorylated peptides are separated and quantified by a Caliper LC3000 system for calculating percent inhibition. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [4]

    AZD1480 is dissolved in DMSO.

    Renca or 786-O cells are suspended in DMEM medium with 5% FBS, and seeded in 96-well plates (5×103 per well) to allow adhesion and then treated with DMSO or AZD1480 for 48 hours. Cell viability is determined by MTS assay. Absorbance at 490 nm is measured with Mikrotek Laborsysteme. Mouse endothelial cells and splenic CD11b+/c- myeloid cells are enriched from tumor-bearing mice,and cultured in 5% FBS RPMI-1640 medium. HUVECs are cultured on collagen 1-coated plates in complete medium. All cells are treated with DMSO and AZD1480 at various doses for 24 hours. Cell viability is determined by counting cell number manually. All the experiments are repeated 3 times. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    AZD1480 is suspended in water supplemented with 0.5% Hypromellose and 0.1% Tween 80. 

    For subcutaneous (s.c.) tumor model, 2.5×106 Renca or 786-O cells suspended in 100 μL PBS are injected into the flank of BALB/c or nude mice, respectively. When average tumor volume reaches approximately 100-150 mm3, AZD1480 or vehicle is administered by oral gavage either once a day at the dose of 50 mg/kg, or twice daily at 30 mg/kg, as indicated. Tumor size is measured by caliper every other day. For experimental lung metastasis model, 0.1×106 Renca or 1×106 786-O cells suspended in 500 μL PBS are injected via tail vein to BALB/c or nude mice, respectively. Three days later, mice are orally treated with AZD1480 (50 mg/kg/d) or vehicle for 21 days for Renca tumors and 60 days for 786-O tumors respectively. For the Calu-6 model, 3×106 tumor cells in matrigel are implanted s.c. into the flanks of nude mice, randomized into vehicle (twice daily, BID) and drug treatment (AZD1480, 30 mg/kg BID) groups, and dosed orally daily for 19 days. For spontaneous lung metastasis model, 2×105 4T1 cells suspended in 100 μL PBS are injected in the mammary gland of female BALB/c mice by gently penetrating the skin. AZD1480 (50 mg/kg/d) or vehicle is given orally for 21 days. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

    Purity: 99.37%

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    AZD-1480
    Cat. No.:
    HY-10193
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