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AZ 960

Cat. No. M1660
AZ 960 Structure
Size Price Availability Quantity
10mg USD 400 In stock
50mg USD 1200 In stock
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Quality Control
Biological Activity

AZ960 is a novel and specific inhibitor of the JAK2 kinase with a Ki of 0.45nM in vitro.  AZ 960 effectively induced growth arrest and apoptosis of human T-cell lymphotropic virus type 1, HTLV-1-infected T cells (MT-1 and MT-2) in parallel with downregulation of the phosphorylated forms of Jak2 and Bcl-2 family proteins including Bcl-2 and Mcl-1.  Importantly, genetic inhibition of Bcl-xL by a small interfering RNA potentiated antiproliferative effects of AZ960 in MT-1 cells. Taken together, Jak2 is an attractive molecular target for treatment of ATL.

Protocol
Cell Experiment
Cell lines SET-2 and TEL-JAK2 Ba/F3 cells
Preparation method Proliferation Assay
Cellular proliferation was evaluated using the fluorometric/colorimetric BIOSOURCE AlamarBlue Assay (Invitrogen) and read in the Spectra Max Gemini EM microplate reader (Molecular Devices, Sunnyvale, CA). SET-2 cells were plated at 20,000 cells/well, TEL-JAK2 Ba/F3 cells at 2000 cells/well, and all other TEL-JAKs at 5000 cells/well in 96-well plates. Cells were treated with compound 24 h after plating and grown for 72 h for SET-2 and 48 h for TEL-JAK Ba/F3 cells. Following the indicated growth period Alamar Blue (10 μl/well) was added, cells were incubated at 37 °C in 5% CO2 for 2 h, and fluorescence was measured at 545 (excitation) and 600 nm (emission). Data are normalized to percent of the control, and GI50 values (the concentration that causes 50% growth inhibition) were calculated using Xlfit4 version 4.2.2 for Microsoft Excel.
Concentrations 0~100 μM
Incubation time 72 h for SET-2 and 48 h for TEL-JAK Ba/F3 cells
Animal Experiment
Animal models
Formulation
Dosages
Administration
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 354.36
Formula C18H16F2N6
CAS Number 905586-69-8
Purity 100.00%
Solubility DMSO
Storage at -20°C
Customer Product Validations & Biological Datas
Source Bioorganic & Medicinal Chemistry (2016) . Figure 6. AZ960 was purchased from Abmole (Catalog No. M1660; Houston, TX)
Method Kinase assays
Cell Lines T. brucei, primary mouse left ventricle smooth muscle cells (vSMC), and rat pancreatic b cells (ins-1)
Concentrations 0.5 and 1 µM
Incubation Time 30 min
Results As shown in Figure 6, treatment of these cells with inhibitor concentrations ranging from 100 nM to 2 mM resulted in dosedependent inhibition of cell growth. The IC50 of AZ960 for mouse ventricular smooth muscle cells was determined to be 25 lM ± 3 and 10 lM ± 1 for rat pancreatic b cells.
Rating
Source Bioorganic & Medicinal Chemistry (2016) . Figure 5. AZ960 was purchased from Abmole (Catalog No. M1660; Houston, TX)
Method Kinase assays
Cell Lines
Concentrations 0.5 and 1 µM
Incubation Time 30 min
Results We calculated the Michaelis–Menten constant (Km) for TbERK8 to be 3.4 lM ± 0.12 (Fig. 5A). The inhibition constant (Ki) of AZ960 for TbERK8 was calculated to be 1.25 lM ± 0.35 (Fig. 5B).
Rating
Source Bioorganic & Medicinal Chemistry (2016) . Figure 4. AZ960 was purchased from Abmole (Catalog No. M1660; Houston, TX)
Method Kinase assays
Cell Lines
Concentrations 1 µM
Incubation Time 30 min
Results As shown in Figure 4, compounds that inhibited TbERK8 kinase activity to 20% or less included AZD5438, PF-03814735, Milciclib, and AZ960. Our studies suggest that SNS-032, NVP-BGT226, GSK2126458, Dinaciclib, and Torin 2 have anti-T. brucei activities with mechanisms that likely do not involve inhibition of TbERK8.
Rating
Source Bioorganic & Medicinal Chemistry (2016) . Figure 3. AZ960 was purchased from Abmole (Catalog No. M1660; Houston, TX)
Method Cell Titer-Glo Promega assay
Cell Lines T. brucei strain WT-221
Concentrations 80 nM to 1 µM
Incubation Time 48 h
Results The inhibitor activities ranged from 80 nM to 1 µM. Dinaciclib was the most potent inhibitor with an IC50 of 80 nM, but SNS-032, GSK2126458, and AZ960 were almost equally as potent with IC50 values of 120 nM, 111 nM, 120 nM, respectively. A representative dose–response curve for AZ960 is shown in Figure 3.
Rating
Source Bioorganic & Medicinal Chemistry (2016) . Figure 2. AZ960 was purchased from Abmole (Catalog No. M1660; Houston, TX)
Method luciferase-based phenotypic screen
Cell Lines T. brucei strain WT-221
Concentrations 1 µM
Incubation Time 48 h
Results A rescreen that tested the select hits demonstrated a dramatic decrease in the mean RLU values by about 2 log10 orders, confirming the antiparasitic activity of the compounds (Fig. 2).
Rating
Product Citations
References

Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia.
Ikezoe et al. Int J Cancer. 2011 Nov 15;129(10):2512-21. PMID: 21207414.

AZ960, a novel Jak2 inhibitor, induces growth arrest and apoptosis in adult T-cell leukemia cells.
Yang et al. Mol Cancer Ther. 2010 Dec;9(12):3386-95. PMID: 21159615.

Effects of the JAK2 inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2.
Gozgit JM, et al. J Biol Chem. 2008 Nov 21;283(47):32334-43. PMID: 18775810.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: AZ 960 supplier, JAK, inhibitors

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