Saururus cernuus lignans - Potent small molecule inhibitors of hypoxia-inducible factor-1

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

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


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 IC 50 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.

Original languageEnglish (US)
Pages (from-to)1026-1033
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Aug 5 2005


  • Breast cancer
  • Dineolignan
  • HIF-1 inhibitor
  • Hypoxia
  • Manassantin
  • Natural product
  • Saururus cernuus
  • Sesquineolignan
  • Small molecule

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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