کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2114271 | 1084527 | 2010 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Differential inhibition sensitivities of MET mutants to the small molecule inhibitor SU11274
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Differential inhibition sensitivities of MET mutants to the small molecule inhibitor SU11274 Differential inhibition sensitivities of MET mutants to the small molecule inhibitor SU11274](/preview/png/2114271.png)
چکیده انگلیسی
Point mutations emerge as one of the rate-limiting steps in tumor response to small molecule inhibitors of protein kinases. Here we characterized the response of the MET mutated variants, V1110I, V1238I, V1206L and H1112L to the small molecule SU11274. Our results reveal a distinct inhibition pattern of the four mutations with IC50 values for autophosphorylation inhibition ranging between 0.15 and 1.5 μM. Differences were further seen on the ability of SU11274 to inhibit phosphorylation of downstream MET transducers such as AKT, ERK, PLCγ and STAT3 and a variety of MET-dependent biological endpoints. In all the assays, H1112L was the most sensitive to SU11274, while V1206L was less affected under the used concentration range. The differences in responses to SU11274 are discussed based on a structural model of the MET kinase domain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 289, Issue 2, 28 March 2010, Pages 228-236
Journal: Cancer Letters - Volume 289, Issue 2, 28 March 2010, Pages 228-236
نویسندگان
Yitzhak Zimmer, Angelina V. Vaseva, Michaela Medová, Bruno Streit, Wieslawa Blank-Liss, Richard H. Greiner, Nikolaus Schiering, Daniel M. Aebersold,