Sulfonamides as a new scaffold for hypoxia inducible factor pathway inhibitors

Academic Article


  • Solid tumors generally grow under hypoxic conditions, a pathophysiological change, which activates the expression of genes responsible for malignant, aggressive, and treatment-refractory properties. Hypoxia inducible factor (HIF) is the chief transcription factor regulating hypoxia-driven gene expression. Therefore, the HIF pathway has become a critical target for cancer therapeutics development. We screened a privileged library of about 10,000 natural-product-like compounds using a cell-based assay for HIF-dependent transcriptional activity and identified several arylsulfonamide HIF pathway inhibitors. Among these compounds, the most potent ones showed an IC 50 of ∼0.5 μM in the hypoxia-responsive element (HRE)-luciferase reporter system. Further studies are needed to fully elucidate the mechanism of action of this class of compounds and their structure-activity relationship. © 2011 Elsevier Ltd. All rights reserved.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Tan C; De Noronha RG; Devi NS; Jabbar AA; Kaluz S; Liu Y; Mooring SR; Nicolaou KC; Wang B; Van Meir EG
  • Start Page

  • 5528
  • End Page

  • 5532
  • Volume

  • 21
  • Issue

  • 18