Bosutinib (SKI-606)
(Synonyms: 伯舒替尼,SKI-606) 目录号 : GC13343
An inhibitor of Src and Abl kinases
Cas No.:380843-75-4
Sample solution is provided at 25 µL, 10mM.
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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.
| 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. | |
| Cas No. | 380843-75-4 | SDF | |
| 别名 | 伯舒替尼,SKI-606 | ||
| 化学名 | 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile | ||
| Canonical SMILES | CN1CCN(CC1)CCCOC2=C(C=C3C(=C2)N=CC(=C3NC4=CC(=C(C=C4Cl)Cl)OC)C#N)OC | ||
| 分子式 | C26H29Cl2N5O3 | 分子量 | 530.45 |
| 溶解度 | ≥ 26.5mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8852 mL | 9.426 mL | 18.8519 mL |
| 5 mM | 0.377 mL | 1.8852 mL | 3.7704 mL |
| 10 mM | 0.1885 mL | 0.9426 mL | 1.8852 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet