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AT7519

Cat. No. M1653
AT7519 Structure
Size Price Availability Quantity
10mg USD 155 In stock
50mg USD 480 In stock
100mg USD 690 In stock
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Quality Control
Biological Activity

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.

Protocol
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)
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 382.24
Formula C16H17Cl2N5O2
CAS Number 844442-38-2
Purity >99%
Solubility DMSO
Storage at -20°C
Customer Product Validations & Biological Datas
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.
Rating
References

Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation.
Alessandri et al. PLoS One. 2011;6(9):e25683. PMID: 21984938.

A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors.
Mahadevan et al. Ann Oncol. 2011 Sep;22(9):2137-43.. PMID: 21325451.

AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples.
Squires et al. Mol Cancer Ther. 2010 Apr;9(4):920-8. PMID: 20354122.

AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition.
Santo L, et al. Oncogene. 2010 Apr 22;29(16):2325-36. PMID: 20101221.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: AT7519 supplier, CDK, inhibitors

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