Synergy and antagonism of promiscuous inhibition in multiple-compound mixtures.
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.
Feng
Brian Y
BY
Department of Pharmaceutical Chemistry and Graduate Group in Chemistry and Chemical Biology, University of California- San Francisco, 1700 4th Street, California 94143-2550, USA.
Shoichet
Brian K
BK
D045424:Complex Mixtures / Q000737:chemistry*; D004336:Drug Antagonism; D004338:Drug Combinations; D015195:Drug Design; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000737:chemistry*; D008433:Mathematics; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry
D045424:Complex Mixtures; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases