All AbMole products are for research use only, cannot be used for human consumption.
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.
Bioorg Med Chem. 2016 Oct 1;24(19):4647-51.
Discovery and antiparasitic activity of AZ960 as a Trypanosoma brucei ERK8 inhibitor
AZ 960 purchased from AbMole
 |
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. |
 |
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). |
 |
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. |
 |
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. |
 |
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). |
| 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 | |
| Molecular Weight | 354.36 |
| Formula | C18H16F2N6 |
| CAS Number | 905586-69-8 |
| Solubility (25°C) | DMSO 60 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related JAK Products |
|---|
| iJak-381
iJak-381 is a JAK1/2 inhibitor with anti-inflammatory activity. |
| Ritlecitinib (malonate)
Ritlecitinib (PF-06651600) malonate is an orally active and selective JAK3 inhibitor with an IC50 of 33.1 nM. |
| Deuruxolitinib
Deuruxolitinib is a deuterated Ruxolitinib (INCB18424), which modulates the activity of JAK1/JAK2. Deuruxolitinib can be used for the research of hair loss disorders. |
| A-005
A-005 is a potentially first-in-class, brain-penetrating TYK2 allosteric inhibitor for studies related to neuroinflammatory and neurodegenerative diseases. |
| Tyrosine Protein Kinase JAK 2 (Phospho-Tyr8, 9)
Tyrosine Protein Kinase JAK 2 (Phospho-Tyr8, 9) is a peptide corresponding to amino acids 475 to 491 of mouse JAK2. |
All AbMole products are for research use only, cannot be used for human consumption or veterinary use. We do not provide products or services to individuals. Please comply with the intended use and do not use AbMole products for any other purpose.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2024 AbMole BioScience. All Rights Reserved.
