Discovery of small molecule inhibitors for the C. elegans caspase CED-3 by high-throughput screening

Biochem Biophys Res Commun. 2017 Sep 23;491(3):773-779. doi: 10.1016/j.bbrc.2017.07.100. Epub 2017 Jul 18.

Abstract

C. elegans has been widely used as a model organism for programmed cell death and apoptosis. Although the CED-3 caspase is the primary effector of cell death in C. elegans, no selective inhibitors have been identified. Utilizing high-throughput screening with recombinant C. elegans CED-3 protein, we have discovered and confirmed 21 novel small molecule inhibitors. Six compounds had IC50 values < 10 μM. From these, four distinct chemotypes were identified. The inhibitor scaffolds described here could lead to the development of selective molecular probes to facilitate our understanding of programmed cell death in this model organism.

Keywords: Apoptosis; C. elegans; CED-3; Caspase; High-throughput screening; Small molecule inhibitor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caenorhabditis elegans Proteins / antagonists & inhibitors*
  • Caspase Inhibitors / analysis*
  • Caspase Inhibitors / chemistry*
  • Caspases
  • Drug Discovery / methods*
  • Drug Evaluation, Preclinical / methods*
  • High-Throughput Screening Assays / methods*
  • Molecular Weight

Substances

  • Caenorhabditis elegans Proteins
  • Caspase Inhibitors
  • Caspases
  • ced-3 protein, C elegans