Bosutinib (SKI-606)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Bosutinib (SKI-606) is a potent inhibitor of Src and Abl kinases with IC50 of 1.2 nM and 1 nM [1].
In chronic myelogenous leukemia (CML) cells, SKI-606 inhibited phosphorylation of Bcr-Abl, Src and Stat5. It also ablated the expression of v-Abl in fibroblasts and blocked proliferation of CML cells [2]. In colorectal cancer cells, SKI-606 inhibited Src autophosphorylation with an IC50 of ~ 0.25 μM, and simultaneity suppressed Tyr (925) phosphorylation of a Src substrate [3]. SKI-606 blocked beta-catenin function by inhibiting its binding to the TCF4 transcription factor and dose-dependently suppressed cyclin D1. SKI-606 increased its binding affinity of beta-catenin to E-cadherin and adhesion, with ensuing reduced motility in a wound healing assay [4].
Oral administration of SKI-606 at 100 mg/kg for 5 days causes complete regression of large K562 xenografts in nude mice [2].
[1]. Boschelli DH, Ye F, Wang YD, Dutia M, Johnson SL, Wu B, Miller K, Powell DW, Yaczko D, Young M, Tischler M, Arndt K, Discafani C, Etienne C, Gibbons J, Grod J, Lucas J, Weber JM, Boschelli F. Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J Med Chem. 2001 Nov 8;44(23):3965-77.
References:
[2]. Golas JM, Arndt K, Etienne C, Lucas J, Nardin D, Gibbons J, Frost P, Ye F, Boschelli DH, Boschelli F. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res. 2003 Jan 15;63(2):375-81.
[3]. Golas JM, Lucas J, Etienne C, Golas J, Discafani C, Sridharan L, Boghaert E, Arndt K, Ye F, Boschelli DH, Li F, Titsch C, Huselton C, Chaudhary I, Boschelli F. SKI-606, a Src/Abl inhibitor with in vivo activity in colon tumor xenograft models. Cancer Res. 2005 Jun 15;65(12):5358-64.
[4]. Coluccia AM, Benati D, Dekhil H, De Filippo A, Lan C, Gambacorti-Passerini C. SKI-606 decreases growth and motility of colorectal cancer cells by preventing pp60(c-Src)-dependent tyrosine phosphorylation of beta-catenin and its nuclear signaling. Cancer Res. 2006 Feb 15;66(4):2279-86.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 530.45 |
| Cas No. | 380843-75-4 |
| Formula | C26H29Cl2N5O3 |
| Solubility | ≥26.5mg/mL in DMSO |
| Chemical Name | 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile |
| SDF | Download SDF |
| Canonical SMILES | CN1CCN(CC1)CCCOC2=C(C=C3C(=C2)N=CC(=C3NC4=CC(=C(C=C4Cl)Cl)OC)C#N)OC |
| Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. |
| Cell experiment: [1] | |
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Cell lines |
MDA-MB-468, MDA-MB-231, MCF-7 and MDA-MB-435 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 μM, 48 hours |
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Applications |
Effects on cell morphology were observed at a concentration of 1 µM SKI-606 for all cell lines examined, and morphological changes were apparent at concentrations as low as 0.25 µM. SKI-606 caused the cells to adhere to each other, forming dense clusters as compared to vehicle control (DMSO) treated cells, which showed spreading over larger areas. |
| Animal experiment: [2] | |
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Animal models |
Female athymic nude mice bearing human pancreas xenografts (P281 or P420) |
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Dosage form |
Oral administration, 100 mg/Kg/d, for 28 days |
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Applications |
Two xenografts, one sensitive (P281) and one resistant (P420), were chosen to assess pharmacodynamic changes by Western blot after treatment with bosutinib. Four different samples were analyzed from P281and P420, and optical scanning was done. The sensitive xenograft P281showed decreased posttreatment Src, STAT-5, p-STAT-5, p-Akt, MAPK, and EGFR. Bosutinib-treated P281showed a marked increase in cleaved PARP. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Vultur A, Buettner R, Kowolik C, et al. SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells. Molecular cancer therapeutics, 2008, 7(5): 1185-1194. [2] Messersmith W A, Rajeshkumar N V, Tan A C, et al. Efficacy and pharmacodynamic effects of bosutinib (SKI-606), a Src/Abl inhibitor, in freshly generated human pancreas cancer xenografts. Molecular cancer therapeutics, 2009, 8(6): 1484-1493. | |
| Description | Bosutinib is a potent dual inhibitor of c-Src and Abl with IC50 values of 1.2 nM and 1 nM, respectively. | |||||
| Targets | c-Src | Abl | ||||
| IC50 | 1.2 nM | 1 nM | ||||
Quality Control & MSDS
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Chemical structure
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