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International Journal of Medicinal Chemistry
Volume 2014, Article ID 237286, 14 pages
Research Article

Development of Small Molecular Proteasome Inhibitors Using a Caenorhabditis elegans Screen

1 Department of Biology, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, USA
2 Department of Chemistry, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, USA

Received 30 May 2014; Revised 6 October 2014; Accepted 8 October 2014; Published 11 November 2014

Academic Editor: Maria Cristina Breschi

Copyright © 2014 Sudhir Nayak et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We have developed a screening protocol to identify compounds with characteristics of small molecule proteasome inhibitors using the real-time analysis of the Caenorhabditis elegans germ line. This screen is able to identify compounds that induce germ line phenotypes characteristic of a reduction in proteasome function such as changes in polarity, aberrant nuclear morphology, and stimulation of apoptosis. This basic protocol is amenable to a high throughput (96-well) format and has been used successfully to identify multiple compounds for further analysis based on structural elements from the naturally occurring compounds lactacystin and the β-lactone homologs omuralide and salinosporamide A. The further development of this assay system should allow for the generation of novel small molecule proteasome inhibitors in a genetically tractable whole animal amenable to biochemical analysis.