Antibodies
Bosutinib (SKI-606)
- 貨號 Cat. No.
- S1014
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
Bosutinib (SKI-606)
Licensed by Pfizer
Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM, respectively.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM, respectively. | |||||
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| Targets | Src | Abl | ||||
| IC50 | 1.2 nM [1] | 1 nM [2] | ||||
| In vitro | Bosutinib is selective for Src over non-Src family kinases with an IC50 of 1.2 nM, and potently inhibits Src-dependent cell proliferation with an IC50 of 100 nM. [1] Bosutinib significantly inhibits the proliferation of Bcr-Abl-positive leukemia cell lines KU812, K562, and MEG-01 but not Molt-4, HL-60, Ramos, and other leukemia cell lines, with IC50 of 5 nM, 20 nM and 20 nM, respectively, more potently than that of STI-571. Similar to STI-571, Bosutinib displays antiproliferative activity against the Abl-MLV-transformed fibroblasts with IC50 of 90 nM. Bosutinib ablates tyrosine phosphorylation of Bcr-Abl and STAT5 in CML cells and of v-Abl expressed in fibroblasts at the concentration of ~50 nM, 10-25 nM and 200 nM, respectively, leading to the Bcr-Abl downstream signaling inhibition of Lyn/Hck phosphorylation. [2] Although unable to inhibit the proliferation and survival of breast cancer cells, Bosutinib significantly decreases the motility and invasion of breast cancer cells with IC50 of ~250 nM, involved with an increase in cell-to-cell adhesion and membrane localization of β-catenin.[3] | |||||
| In vivo | Bosutinib (60 mg/kg/day) is active against Src-transformed fibroblasts xenografts and HT29 xenografts in nude mice with T/C of 18% and 30%, respectively. [1] Oral administration of Bosutinib for 5 days significantly suppresses K562 tumor growth in mice in a dose-dependent manner, with the large tumors eradicated at dose of 100 mg/kg and tumor free at 150 mg/kg without overt toxicity. [2] As being inactive against Colo205 xenografts in nude mice at 50 mg/kg twice daily, Bosutinib dosing at 75 mg/kg twice daily is necessary against Colo205 xenografts, and increasing the dose of Bosutinib has no additional benefit, in contrast to the significant dose-dependent ability against HT29 xenografts. [4] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay:
| The Src and Abl kinase assays | The Src kinase activity is measured in an ELISA format. Src (3 units/reaction), reaction buffer (50 mM Tris-HCl pH 7.5, 10 mM MgCl2, 0.1 mM EGTA, 0.5 mM Na3VO4) and cdc2 substrate peptide are added to various concentration of Bosutinib and incubated at 30 °C for 10 minutes. The reaction is started by the addition of ATP to a final concentration of 100 μM, incubated at 30 °C for 1 hour and stopped by addition of EDTA. Instructions from the manufacturer are followed for subsequent steps. The Abl kinase assay is performed in a DELFIA solid phase europium-based detection assay format. Biotinylated peptide (2 μM) is bound to streptavidin-coated microtitration plates for 1.5 hours in 1 mg/mL ovalbumin in PBS. The plates are washed for 1 hour with PBS/0.1% Tween 80, followed by a PBS wash. The kinase reaction is incubated for 1 hour at 30°C. Abl kinase (10 units) is mixed with 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 80 μM EGTA, 100 μM ATP, 0.5 mM Na3VO4, 1% DMSO, 1 mM HEPES (pH 7.0), 200 μg/mL ovalbumin and various concentration of Bosutinib. The reaction is stopped with EDTA at a final concentration of 50 mM. The reaction is monitored with Eu-labeled phosphotyrosine antibody and DELFIA enhancement solution. |
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Cell Assay:
| Cell lines | Abl-MLV, Rat 2, KU812, K562, and MEG-01 cells |
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| Concentrations | Dissolved in DMSO, final concentrations ~1 μM |
| Incubation Time | 72 hours |
| Method | Cells are exposed to various concentrations of Bosutinib for 72 hours. Anchorage-independent proliferation of Abl-MLV-transformed fibroblasts is measured in 96-well ultra-low binding plates treated with Sigmacote to block residual cell attachment. Cell proliferation is measured with MTS or Cell-Glo. For the determination of cell cycle or cell death, cells are prepared for FACS analysis in the CycleTest Plus DNA reagent kit and analyzed on a fluorescence-activated cell sorter flow cytometer. |
Animal Study:
| Animal Models | Nude female mice injected with K562 cells |
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| Dosages | ~150 mg/kg/day |
| Administration | Oral gavage |
References
Chemical Information
Download Bosutinib (SKI-606) SDF
| Molecular Weight (MW) | 530.45 |
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| Formula | C26H29Cl2N5O3 |
| CAS No. | 380843-75-4 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 100 mg/mL (188 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 2 mg/mL (3 mM) | ||
| * <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-(2,4-dichloro-5-methoxyphenylamino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.53045 | 5.3045 | 10.609 | 15.9135 |
Customer Reviews (3)
 Click to enlarge | Rating | |
| Source | J Biol Chem 2010 285, 7977–7985. Bosutinib (SKI-606) purchased from Selleck | |
| Method | Western blot | |
| Cell Lines | Mouse sperm | |
| Concentrations | 0-50 μM | |
| Incubation Time | 60 min | |
| Results | In the case of SKI606, a sharp inhibitory effect was observed at 50 μM. |
Product Citations (5)
KIT-D816V–independent oncogenic signaling in neoplastic cells in systemic mastocytosis: role of Lyn and Btk activation and disruption by dasatinib and bosutinib. [Gleixner KV, et al. Blood 2011;118(7):1885-98]
CAV1 inhibits metastatic potential in melanomas through suppression of the integrin/Src/FAK signaling pathway. [Trimmer C, et al. Cancer Res 2010;70(19):7489-99]
Identification of a Src tyrosine kinase/SIAH2 E3 ubiquitin ligase pathway that regulates C/EBPδ expression and contributes to transformation of breast tumor cells. [Sarkar TR, et al. Mol Cell Biol 2012;32(2):320-32]
