Item

Specification

Appearance

white to beige powder

Solubility

Soluble in chloroform (slightly heated), DMSO (slightly heated), methanol (slightly heated)

Nuclear magnetic resonance (NMR)

structurally consistent

High performance liquid chromatography (HPLC)

>98%

Product Description

AZD 1480 is a novel ATP competitive JAK2 inhibitor with an IC50 of 0.26 nM in cell-free assays. It selectively acts on JAK3 and Tyk2, but has a weaker effect on JAK1. Phase 1。

Target point

JAK2 [1]
(Cell-free assay)

0.26 nM

In vitro research

5 μ M AZD1480 induces cell cycle arrest at G2/M phase and induces cell death by inhibiting Aurora kinase. it is an effective inhibitor of JAK2 that acts on human multiple myeloma cells, inhibiting growth, survival, FGFR3 and STAT3 signaling, as well as downstream targets including Cyclin D2. At low micromolar concentrations, it inhibits cell proliferation and induces apoptosis in myeloma cell lines. it acts on human and mouse glioma cells, effectively inhibiting the phosphorylation of constitutive and inducible JAK1, JAK2, and STAT-3, resulting in reduced cell proliferation and induction of apoptosis. it is an effective ATP competitive JAK1/2 kinase small molecule inhibitor that can inhibit STAT3 phosphorylation and tumor growth, and this inhibition is STAT3 dependent. it inhibits tumor angiogenesis and local metastasis by affecting the tumor microenvironment.

In vivo research

AZD1480 acts on human solid tumor models and multiple myeloma models, inhibiting STAT3 phosphorylation.  In vivo, it inhibits the growth of subcutaneous transplanted tumors and increases the lifespan of mice carrying intracranial malignant gliomas (GBM) by inhibiting STAT3 activity, indicating that the pharmacology of AZD1480 inhibiting the JAK/STAT3 pathway can be used to study the treatment of patients carrying intracranial malignant gliomas. it inhibits lung infiltration and lung metastasis of bone marrow cells. it acts on a human transplant tumor model to reduce angiogenesis and metabolism. it inhibits the growth of human solid tumors containing STAT activity.

characteristic

AZD1480 is a potential novel therapeutic agent for the treatment of multiple myeloma.

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

50 mM

0.0573 mL

0.2867 mL

0.5734 mL

Kinase experiment

Under the conditions of buffer (including 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween-20, 50 µ g/ml BSA, and 10 mM MgCl2), the inhibitory effect of recombinant Jak1, Jak2, or Jak3 on AZD1480 was studied. In insect cells, Jak3 enzyme is expressed as a nitrogen terminal GST fusion protein and purified by glutathione affinity and size exclusion chromatography. Add it (10 point dose-response, repeated three times, 8.3 µ M to 0.3 nM) and perform enzyme experiments using 1.5 µ M peptide substrates (Jak1: FITC-C6-KKHTDDGYMPSMPSGVA-NH2, Jak2 and Jak3: FAM-SRCtide) and their respective ATP Km (Jak1: 55 µ M, Jak2: 15 µ M, Jak3: 3 µ M) at an ATP concentration of 5 mM. Separate phosphorylated and non phosphorylated peptide segments and calculate the inhibition percentage using the Caliper LC3000 system.

Cell experiment

Cell line

Renca or 786-O cells, mouse endothelial cells and splenic CD11b+/c-bone marrow cells, HUVECs

concentration

1 μM

processing time

48 or 24 hours

method

Renca or 786-O cells were suspended in DMEM medium containing 5% FBS, and seeded onto a 96 well plate with 5 × 103 cells per well to allow cell adhesion. The experimental group was treated with it, while the control group was treated with DMSO for 48 hours. Measure cell viability through MTS experiment. Measure the absorbance at 490nm using Mikrotek Laborsysteme. Mouse endothelial cells and splenic CD11b+/c-bone marrow cells were enriched from tumor carrying mice and cultured on RPMI-1640 medium containing 5% FBS. HUVECs were cultured on collagen coated plates containing complete culture medium. Treat all cells with DMSO and different doses of AZD1480 for 24 hours. Manually calculate the number of cells and measure cell viability. All experiments were repeated three times.

Animal experiments

animal model

Female BALB/c and athymic mice (NCR-nu/nu) (7-8 weeks old)

dose

Once a day, at a dose of 50 mg/kg; Or twice a day at a dose of 30 mg/kg

Medication treatment

Oral feeding

Packing：

1kg/foil bag;5kg/carton;25kg/fiber drum; or packing as your request.

Customization:

l Customized logo

l Customized packaging

l Graphic customization

Shipping：

By Courier; By Air or By Sea, according to your demands