Antibodies
BMS-265246
- 貨號 Cat. No.
- S2014
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
BMS-265246
Catalog No.S2014
BMS-265246 is a potent and selective CDK1/2 inhibitor with IC50 of 6 nM/9 nM. It is 25-fold more selective for CDK1/2 than CDK4.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | BMS-265246 is a potent and selective CDK1/2 inhibitor with IC50 of 6 nM/9 nM. It is 25-fold more selective for CDK1/2 than CDK4. | |||||
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| Targets | CDK1/cyclin B | CDK2/cyclin E | ||||
| IC50 | 6 nM | 9 nM [1] | ||||
| In vitro | BMS265246 inhibits the activity of CDK4/cycD with IC50 of 0.23 μM and prevents A2780 Cytox with IC50 of 0.76 μM. BMS265246 which binds to CDK2 shows the inhibitor resides coincident with the ATP purine binding site and forms important H-bonds with Leu83 on the protein backbone. BMS265246 exhibits CDK1 and CDK2 potency that is 25- and 11-fold more potent versus CDK1 and CDK2, respectively. BMS265246 represents the most potent CDK/CDK2 selective analogue from this chemotype. [1] A recent study shows that BMS-265246 inhibits cell proliferation with EC50 ranging from 0.293 μM-0.492 μM in HCT-116 cells. After treatment of BMS-265246, the dominant cell populations are G2-arrested cells having 4N DNA content, large round nuclei, and low DNA intensity. [2] | |||||
| In vivo | ||||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| CDK1/Cyclin B1 Kinase Assay | Kinase reactions consists of 100 ng of baculovirus expressed GST-CDK1/cyclin B1 complex, 1 μg histone H1, 0.2 μCi 33P γ-ATP, 25 μM ATP in 50 μL of kinase buffer (50 mM Tris, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 0.5 mM DTT). Reactions are incubated for 45 min at 30 °C and stopped by the addition of cold trichloroacetic acid (TCA) to a final concentration of 15%. TCA precipitates are collected onto GF/C unifilter plates using a Filtermate universal harvester, and the filters are quantitated using a TopCount 96 well liquid scintillation counter. Dose response curves are generated to determine the concentration required to inhibit 50% of kinase activity (IC50). BMS265246 is dissolved at 10 mM in DMSO and evaluated at six concentrations, each in triplicate. The final concentration of DMSO in the assay equals 2%. IC50 values are derived by nonlinear regression analysis and have a coefficient of variance (SD/mean, n = 6) = 16%. |
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| CDK2/Cyclin E Kinase Assay | Kinase reactions consists of 5 ng of baculovirus expressed GST-CDK2/cyclin E complex, 0.5 μg GST-RB fusion protein (amino acids 776−928 of retinoblastoma protein), 0.2 μCi 33P γ-ATP, and 25 μM ATP in 50 μL of kinase buffer (50 mM HEPES, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT). Reactions are incubated for 45 min at 30 °C and stopped by the addition of cold TCA to a final concentration of 15%. TCA precipitates are collected onto GF/C unifilter plates using a Filtermate universal harvester, and the filters are quantitated using a TopCount 96 well liquid scintillation counter. Dose response curves are generated to determine the concentration required inhibiting 50% of kinase activity (IC50). BMS265246 is dissolved at 10 mM in DMSO and evaluated at six concentrations, each in triplicate. The final concentration of DMSO in the assay equals 2%. IC50 values are derived by nonlinear regression analysis and have a coefficient of variance (SD/mean, n = 6) = 14%. |
Cell Assay: [2]
| Cell lines | HCT116 |
|---|---|
| Concentrations | 0-5 μM |
| Incubation Time | 24 hours |
| Method | HCT-116 cells are plated onto 96-well dishes. For each well, the cell density is calculated by counting the number of objects (cells) per field of view, and averaging across all fields for a given well. For a treatment compound, cell density is converted to a percentage relative to the plate-averaged cell density from DMSO treatment (i.e., 100% corresponds to the average cell density for DMSO treatment). Logistic regression curve fits are done using TIBCO Spotfire, and the concentration at which the curve crosses 50% is reported as the EC50 of BMS-265246. |
References
Chemical Information
| Molecular Weight (MW) | 345.34 |
|---|---|
| Formula | C18H17F2N3O2 |
| CAS No. | 582315-72-8 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 20 mg/mL (57 mM) |
|---|---|---|---|
| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | (4-butoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)(2,6-difluoro-4-methylphenyl)methanone |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.34534 | 3.4534 | 6.9068 | 10.3602 |
