کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10769850 | 1050825 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Saururus cernuus lignans-Potent small molecule inhibitors of hypoxia-inducible factor-1
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Saururus cernuus lignans-Potent small molecule inhibitors of hypoxia-inducible factor-1 Saururus cernuus lignans-Potent small molecule inhibitors of hypoxia-inducible factor-1](/preview/png/10769850.png)
چکیده انگلیسی
Hypoxia-inducible factor-1 (HIF-1) represents an important tumor-selective therapeutic target for solid tumors. In search of novel small molecule HIF-1 inhibitors, 5400 natural product-rich extracts from plants, marine organisms, and microbes were examined for HIF-1 inhibitory activities using a cell-based reporter assay. Bioassay-guided fractionation and isolation, followed by structure elucidation, yielded three potent natural product-derived HIF-1 inhibitors and two structurally related inactive compounds. In a T47D cell-based reporter assay, manassantin B1, manassantin A, and 4-O-methylsaucerneol inhibited hypoxia-induced HIF-1 activation with IC50 values of 3, 3, and 20 nM, respectively. All three compounds are relatively hypoxia-specific inhibitors of HIF-1 activation, in comparison to other stimuli. The hypoxic induction of HIF-1 target genes CDKN1A, VEGF, and GLUT-1 were also inhibited. These compounds inhibit HIF-1 by blocking hypoxia-induced nuclear HIF-1α protein accumulation without affecting HIF-1α mRNA levels. In addition, preliminary structure-activity studies suggest specific structural requirements for this class of HIF-1 inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 333, Issue 3, 5 August 2005, Pages 1026-1033
Journal: Biochemical and Biophysical Research Communications - Volume 333, Issue 3, 5 August 2005, Pages 1026-1033
نویسندگان
Chowdhury Faiz Hossain, Yong-Pil Kim, Scott R. Baerson, Lei Zhang, Richard K. Bruick, Kaleem A. Mohammed, Ameeta K. Agarwal, Dale G. Nagle, Yu-Dong Zhou,