Bosutinib/SKI-606；伯舒替尼
货号：
IB0740
品牌：
Jinpan
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产品简介
| MDL | MFCD07367846 |
| EC | EINECS 700-455-1 |
| 别名 | 博舒替尼;波舒替尼;SKI606 |
| 英文名称 | Bosutinib/SKI-606 |
| CAS | 380843-75-4 |
| 分子式 | C26H29Cl2N5O3 |
| 分子量 | 530.45 |
| 纯度 | ≥99% |
| 单位 | 瓶 |
| 生物活性 | Bosutinib（SKI-606） is a dual Src/Abl inhibitor with IC50s of 1.2 nM and 1 nM, respectively.[1] |
| IC50 | Src: 1.2 nM; Abl: 1 nM[1] |
| In Vitro | SKI-606 (bosutinib), a selective Src family kinase inhibitor, on human cancer cells derived from breast cancer patients to assess its potential for breast cancer treatment. The results show that SKI-606 caused a decrease in cell motility and invasion of breast cancer cell lines with an IC50 of f250 nmol/L, which was also the IC50 for inhibition of cellular Src kinase activity in intact tumor cells. These changes were accompanied by an increase in cell-to-cell adhesion and membrane localization of B-catenin. Analysis of downstream effectors of Src revealed that SKI-606 inhibits the phosphorylation of focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (Pyk2), and Crk-associated substrate (p130Cas), with an IC50 similar to inhibition of cellular Src kinase. SKI-606 inhibits signaling pathways involved in controlling tumor cell motility and invasion, suggesting that SKI-606 is a promising therapeutic for breast cancer.[2] SKI-606, a potent inhibitor of Src and Abl kinases. SKI-606 inhibited Src autophosphorylation with an IC(50) of approximately 0.25 micromol/L in HT29 cells. Phosphorylation of Tyr(925) of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. [3] |
| In Vivo | On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of approximately 3 micromol/L, an oral bioavailability of 18%, and a t(1/2) of 8.6 hours were observed. SKI-606 was orally active in s.c. colon tumor xenograft models and caused substantial reductions in Src autophosphorylation on Tyr(418) in HT29 and Colo205 tumors. SKI-606 inhibited HT29 tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 tumor growth. [3] |
| SMILES | CN1CCN(CC1)CCCOC2=C(C=C3C(NC4=CC(OC)=C(C=C4Cl)Cl)=C(C=NC3=C2)C#N)OC |
| 靶点 | Src |
| 动物实验 | In HT29 xenograft studies, SKI-606 was given by oral gavage once daily to mice with tumors ranging from 200 to 300mg. A dose-dependent antitumor response was observed in those mice given doses of 25 to 150 mg/kg over a 21-day period (P < 0.003 in Student’s two-tailed t test in the group that received the 25 mg/kg/d). Although the once daily 25 mg/kg dose was not consistently active, the higher doses were reproducibly effective. No deaths occurred and no weight loss was observed in animals given SKI-606 at 150 mg/kg. [3] |
| 细胞实验 | Briefly, f5,000 cells were seeded in each well of a 96-well plate and allowed to adhere before the addition of 0.01% DMSO or 0.1, 0.3, and 1 umol/L of SKI-606. After 2to 6 d of incubation at 37℃ in 5% CO2, MTS reagent was added to each well for 30 min and absorbance measured at 490 nm.[2] |
| 数据来源文献 | [1]. Boschelli DH, et al. Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J Med Chem, 2001, 44(23), 3965-3977. [2]. Vultur A, et al. SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells. Mol Cancer Ther, 2008, 7(5), 1185-1194. [3]. Golas JM, et al. SKI-606, a Src/Abl inhibitor with in vivo activity in colon tumor xenograft models. Cancer Res, 2005, 65(12), 5358-5364. |
| 规格 | 10mg 20mg 100mg |
Bosutinib是 Src/Abl 的双抑制剂。