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

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 ?M. 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.

SUBMITTER: Brantley SJ

PROVIDER: S-EPMC5590106 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Brantley Scott J SJ Cotten Steven W SW Lamson David R DR Smith Ginger R GR Liu Rihe R Williams Kevin P KP

Biochemical and biophysical research communications 20170718 3

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 IC<sub>50</sub> values < 10 μM. From these, four distinct chemotypes were identified. The inhibitor scaffolds descr ...[more]

PMID: 28733033

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