Natural-Product-Derived Transient Receptor Potential Melastatin 8 (TRPM8) Channel Modulators
Date
2016-01
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Abstract
A library of novel structural hybrids of menthol and cubebol was tested for each derivative's ability to interact with the transient receptor potential subfamily melastatin member 8 (TRPM8) channel. This structure-activity relationship study revealed three potent modulators of the TRPM8 ion channel: a novel agonist (4) with an EC50 value of 11 ± 1 μM, an antagonist (15) with an IC50 value of 2 ± 1 μM, and an allosteric modulator (21) that minimized channel desensitization toward menthol. Each of these novel exocyclic olefin analogues of menthol is readily accessible by synthesis and was tested using Ca(2+) assays and electrophysiology.
Description
Keywords
Calcium, Alcohols, Reaction products, Modulators, Pharmaceuticals
Citation
LeGay, C. M., Gorobets, E., Iftinca, M., Ramachandran, R., Altier, C., & Derksen, D. J. (2016). Natural-product-derived transient receptor potential melastatin 8 (TRPM8) channel modulators. Organic letters, 18(11), 2746-2749.