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- W1965899527 abstract "The natural calcitonin (CT) receptor and its peptide agonists are considered validated targets for drug discovery. A small molecule agonist, SUN-B8155, has previously been shown to efficiently activate cellular CTR. Herein, we report the synthesis of a series of compounds (S8155 1-9) derived from SUN-B8155, and investigate the structural-functional relationship, bias properties and their cellular activity profile. We discover that the N-hydroxyl group from the pyridone ring is required for G protein activity and its affinity to the CT receptor. Among the compounds studied, S8155-7 exhibits improved G protein activity while S8155-4 displays a significant β-arrestin-2 signaling bias. Finally, we show that both S8155-4 and S8155-7 inhibit tumour cell invasion through CTR activation. These two compounds are anticipated to find extensive applications in chemical biology research as well drug development efforts targeting CT receptor." @default.
- W1965899527 created "2016-06-24" @default.
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- W1965899527 date "1999-05-01" @default.
- W1965899527 modified "2023-10-18" @default.
- W1965899527 title "Calcitonin, an update" @default.
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- W1965899527 doi "https://doi.org/10.1016/s8756-3282(99)00068-x" @default.
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