Synergy and antagonism of promiscuous inhibition in multiple-compound mixtures

J Med Chem. 2006 Apr 6;49(7):2151-4. doi: 10.1021/jm060029z.

Abstract

Screening in mixtures is a common approach for increasing the efficiency of high-throughput screening. Here we investigate how the "compound load" of mixtures influences promiscuous aggregate-based inhibition. We screened 764 molecules individually and in mixtures of 10 at 5 miccroM each, comparing the observed inhibition of the mixtures to that predicted from single-compound results. Synergistic effects on aggregation predominated, although antagonism was also observed. These results suggest that screening mixtures can increase aggregation-based inhibition in a nonadditive manner.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Complex Mixtures / chemistry*
  • Drug Antagonism
  • Drug Combinations
  • Drug Design
  • Drug Synergism
  • Enzyme Inhibitors / chemistry*
  • Mathematics
  • Pharmaceutical Preparations / chemistry*
  • beta-Lactamase Inhibitors
  • beta-Lactamases / chemistry

Substances

  • Complex Mixtures
  • Drug Combinations
  • Enzyme Inhibitors
  • Pharmaceutical Preparations
  • beta-Lactamase Inhibitors
  • beta-Lactamases