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

  • Bioorg Med Chem Lett. 2008 Jan 1;18(1):329-35. doi: 10.1016/j.bmcl.2007.10.100.
Yuli Xie  1 ,  ShiXian Deng ,  Craig J Thomas ,  Yidong Liu ,  Ya-Qin Zhang ,  Alison Rinderspacher ,  Wenwei Huang ,  Gangli Gong ,  Michael Wyler ,  Efithia Cayanis ,  Nathalie Aulner ,  Udo Többen ,  Caty Chung ,  Sergey Pampou ,  Noel Southall ,  Dusica Vidović ,  Stephan Schürer ,  Lars Branden ,  R Eric Davis ,  Louis M Staudt ,  James Inglese ,  Christopher P Austin ,  Donald W Landry ,  Deborah H Smith ,  Douglas S Auld
Affiliations
  • 1. Division of Clinical Pharmacology & Experimental Therapeutics, Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
PMID: 18024113 DOI: 10.1016/j.bmcl.2007.10.100
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.