Structure-Activity Relationship Studies of the Cyclic Depsipeptide Natural Product YM-254890, Targeting the Gq Protein

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Extracellular signals perceived by G protein-coupled receptors are transmitted via G proteins, and subsequent intracellular signaling cascades result in a plethora of physiological responses. The natural product cyclic depsipeptides YM-254890 and FR900359 are the only known compounds that specifically inhibit signaling mediated by the Gq subfamily. In this study we exploit a newly developed synthetic strategy for this compound class in the design, synthesis, and pharmacological evaluation of eight new analogues of YM-254890. These structure-activity relationship studies led to the discovery of three new analogues, YM-13, YM-14, and YM-18, which displayed potent and selective Gq inhibitory activity. This provides pertinent information for the understanding of the Gq inhibitory mechanism by this class of compounds and importantly provides a pathway for the development of labeled YM-254890 analogues.

Original languageEnglish
Issue number11
Pages (from-to)830-834
Number of pages5
Publication statusPublished - 7 Jun 2017

    Research areas

  • Journal Article

ID: 179171087