(−)-FR182877 Is a Potent and Selective Inhibitor of Carboxylesterase-1

Authors

  • Gregory C. Adam,

    1. The Skaggs Institute for Chemical Biology and The Departments of Chemistry and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-8023
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    • These authors contributed equally to this work.

  • Christopher D. Vanderwal,

    1. The Skaggs Institute for Chemical Biology and The Departments of Chemistry and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-8023
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    • These authors contributed equally to this work.

  • Erik J. Sorensen Prof.,

    1. The Skaggs Institute for Chemical Biology and The Departments of Chemistry and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-8023
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  • Benjamin F. Cravatt Prof.

    1. The Skaggs Institute for Chemical Biology and The Departments of Chemistry and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-8023
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  • This research was supported by the NIH (CA87660 and CA085526) and the Skaggs Institute for Chemical Biology.

Abstract

original image

Activity-based profiling and reporter-group-tagged compounds were used to identify carboxylesterase-1 (CE-1) as a specific target of the natural product (−)-FR182877 (see scheme). Now that a target is known, specific modification of the lactone natural product may lead to even more effective inhibitors of CE-1.

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