Identification of N-(quinolin-8-yl)benzenesulfonamides as agents capable of down-regulating NFkappaB activity within two separate high-throughput screens of NFkappaB activation.

Methods Development
Medicinal Chemistry

Abstract

We describe here a series of N-(quinolin-8-yl)benzenesulfonamides capable of suppressing the NFkappaB pathway identified from two high-throughput screens run at two centers of the NIH Molecular Libraries Initiative. These small molecules were confirmed in both primary and secondary assays of NFkappaB activation and expanded upon through analogue synthesis. The series exhibited potencies in the cell-based assays at as low as 0.6 microM, and several indications suggest that the targeted activity lies within a common region of the NFkappaB pathway.

Authors

Xie, Yuli; Deng, ShiXian; Thomas, Craig; Liu, Yidong; Zhang, Ya-Qin; Rinderspacher, Alison; Huang, Wenwei; Gong, Gangli; Wyler, Michael; Cayanis, Efithia; Aulner, Nathalie; Többen, Udo; Chung, Caty; Pampou, Sergey; Southall, Noel; Vidović, Dusica; Schürer, Stephan; Branden, Lars; Davis, R Eric; Staudt, Louis M; Inglese, James; Austin, Christopher; Landry, Donald W; Smith, Deborah H; Auld, Douglas S;

Keywords

  • Combinatorial Chemistry Techniques
  • Down-Regulation/ drug effects
  • NF-kappa B/ antagonists & inhibitors
  • NF-kappa B/ metabolism
  • Quinolines/ chemistry
  • Quinolines/ pharmacology
  • Structure-Activity Relationship
  • Sulfonamides/ chemistry
  • Sulfonamides/ pharmacology

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