کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1393038 1501175 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sorafenib derivatives induce apoptosis through inhibition of STAT3 independent of Raf
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Sorafenib derivatives induce apoptosis through inhibition of STAT3 independent of Raf
چکیده انگلیسی

STAT3 is a transcription factor that modulates survival-directed transcription. It is persistently activated in many human cancers. Literature has shown that sorafenib, Raf kinase inhibitor, reduces Phospho-STAT3 and induces cell death. A series of sorafenib derivatives were synthesized as new inhibitors for STAT3. Urea, sulfonamide, and carboxamide linkers brought out different SARs from the end of sorafenib. Urea and carboxamide linked derivatives showed greater inhibition against STAT3 activity than sulfonamide linked derivatives. In particular, 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(4-cyanophenoxy)phenyl)urea (1), a urea linker, was as potent as sorafenib in reducing P-STAT3 level and cell death but no inhibition for Raf activity. Such result provides a new lead for the design of STAT3 inhibitors.

Sorafenib derivative was synthesized with two steps. It has no inhibition against Raf kinase and contains ability to reduce STAT3 activity. We generated a series of derivatives to test the their ability to reduce P-STAT3.Figure optionsDownload as PowerPoint slideHighlights
► Sorafenib and sorafenib derivative have the cytotoxicity against HCC.
► Both compounds have inhibition in STAT3.
► The derivative has no inhibition in Raf kinase, a target of sorafenib.
► A series of derivatives were synthesized with two steps and tested for STAT3 inhibition in HCC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 46, Issue 7, July 2011, Pages 2845–2851
نویسندگان
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