Bosutinib (SKI-606)
Bosutinib (SKI-606; CAS 380843-75-4) is a dual inhibitor targeting c-Src and Abl kinases with IC50 values of approximately 1.2 nM and 1 nM, respectively. It suppresses phosphorylation of Bcr-Abl, Src, and Stat5 in chronic myeloid leukemia (CML) cells, thereby decreasing proliferation and inducing regression in K562 xenograft tumor models. Bosutinib also reduces Src autophosphorylation and inhibits β-catenin signaling by blocking its interaction with TCF4 transcription factor, consequently downregulating cyclin D1 expression in colorectal cancer cells. This mechanism results in decreased cell motility and enhanced β-catenin binding to E-cadherin, highlighting utility in cancer research.
- 1. Panagi I, Jennings E, et al. "Salmonella Effector SteE Converts the Mammalian Serine/Threonine Kinase GSK3 into a Tyrosine Kinase to Direct Macrophage Polarization." Cell Host Microbe. 2020;27(1):41–53.e6. PMID:31862381
- 2. Alzubi MA, Turner TH, et al. "Separation of breast cancer and organ microenvironment transcriptomes in metastases." Breast Cancer Res. 2019 Mar 6;21(1):36. PMID:30841919
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 530.45 |
| Cas No. | 380843-75-4 |
| Formula | C26H29Cl2N5O3 |
| Solubility | ≥26.5 mg/mL in DMSO; insoluble in H2O; ≥2.16 mg/mL in EtOH with ultrasonic |
| 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 | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| 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. |
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| 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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