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AT7519 is a novel small molecule multi-cyclin-dependent kinase inhibitor.AT7519 displays potent cytotoxicity and apoptosis; associated with in vivo tumor growth inhibition and prolonged survival. At the molecular level, AT7519 inhibited RNA polymerase II (RNA pol II) phosphorylation, a CDK9, 7 substrate, associated with decreased RNA synthesis confirmed by [ (3)H] Uridine incorporation. In addition, AT7519 inhibited glycogen synthase kinase 3beta (GSK-3beta) phosphorylation.
Front Oncol. 2022 Jul 28;12:968547.
Comprehensive analysis of the glutathione S-transferase Mu (GSTM) gene family in ovarian cancer identifies prognostic and expression significance
AT7519 purchased from AbMole
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Source | Oncotarget (2017). Figure 6. AT7519 |
| Method | Cell viability | |
| Cell Lines | CRC cells | |
| Concentrations | 10 μM | |
| Incubation Time | 24 or 48 h | |
| Results | The results from the above experiment are summarized in Figure 6A. 20-223 and AT7519 both effectively arrested the CRC cells in either the G2 or S phase of the cell cycle. |
| Cell Experiment | |
|---|---|
| Cell lines | MM cell lines (MM.1S, U266, OPM1, RPMI, LR5, DOX 40, MM.1R) and primary CD138+ MM cells |
| Preparation method | Cell viability and proliferation assays. AT7519's effects on viability of MM cell lines, primary MM cells, and PBMNCs was assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrasodium bromide (MTT; Chemicon International) dye absorbance as previously described (Raje et al., 2009). DNA synthesis was measured by tritiated thymidine uptake (3H-TdR; Perkin Elmer). MM cells (2–3 × 104cells/well) were incubated in 96-well culture plates (Costar, Cambridge, MA) with media and different concentrations of AT7519 and/or recombinant IL-6 (10 ng/mL) or IGF-1 (50 ng/mL) for 24 or 48 h at 37°C and 3H-TdR incorporation was measured as previously described (Raje et al., 2009). |
| Concentrations | 0~2 μM |
| Incubation time | 48 h |
| Animal Experiment | |
|---|---|
| Animal models | MM xenograft mouse model |
| Formulation | dissolved in saline 0.9% |
| Dosages | 15 mg/kg once a day for five days for 2 weeks |
| Administration | intraperitoneally (IP) |
| Molecular Weight | 382.24 |
| Formula | C16H17Cl2N5O2 |
| CAS Number | 844442-38-2 |
| Solubility (25°C) | DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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