CVT-313 is a potent, selective, reversible, and ATP-competitive inhibitor of CDK2 wirh IC50 of 0.5 μM. Inhibition is competitive with respect to ATP (Ki=95 nM), and selective CVT-313 has no effect on other, nonrelated ATP-dependent serine/threonine kinases. When added to CDK1 or CDK4, a 8.5- and 430-fold higher concentration of CVT-313 is required for half-maximal inhibition of the enzyme activity.
Using normal and tumor human/murine cell lines, the effects of CVT-313 on cell proliferation is measured. The IC50 for growth inhibition ranged from 1.25 to 20 μM. CVT-313 is a promising candidate for evaluation in other disease models related to aberrant cell proliferation.
|Cell lines||MRC-5 cells|
|Preparation method||CVT-313 is prepared in DMSO and stored, and then diluted with appropriate medium before use.
MRC-5 cells are grown in Dulbecco’s modified Eagle’s medium containing 5% fetal calf serum. CVT-313 (0, 5, 10, 15 μM) is added to exponentially growing cells in tissue culture. Cell population is measured. Proliferation assays are carried out using the nonradioactive CellTiter 96 kit after 48-h exposure. For FACS analysis of DNA content, cells are trypsinized, fixed in 70% ice-cold ethanol, and treated with 0.1 mg/mL RNase A and 40 μg/mL propidium iodide for 1 h at 37°C.
|Concentrations||0, 5, 10, 15 μM|
|Incubation time||48 h|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|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.
|Solubility||DMSO 10 mM|
Cell cycle-dependent phosphorylation of human CDC5 regulates RNA processing.
Graub R, et al. Cell Cycle. 2008 Jun 15;7(12):1795-803. PMID: 18583928.
CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation.
Brooks EE, et al. J Biol Chem. 1997 Nov 14;272(46):29207-11. PMID: 9360999.
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Voruciclib (P1446A-05) is a protein kinase inhibitor specific for the cyclin-dependent kinase 4 (CDK4) with IC50s of 90nM, 25nM, and 22nM for CDK4-CyclinD1, CDK1-Cyclin B, and CDK9-Cyclin T, respectively.
ON123300 is a potent inhibitor of CDK4, with an IC50 of 3.8 nM, with little inhibitory activity against CDKs 1,2,5 and 8.
|SCH 900776 (CAS:891494-64-7)
MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2.
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