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Review
. 2019 May 28;20(11):2618.
doi: 10.3390/ijms20112618.

Recent Progress in TRPM8 Modulation: An Update

Rosario González-Muñiz  1 , M Angeles Bonache  2 , Cristina Martín-Escura  3 , Isabel Gómez-Monterrey  4
Affiliations
Review

Recent Progress in TRPM8 Modulation: An Update

Rosario González-Muñiz et al. Int J Mol Sci. .

Abstract

The transient receptor potential melastatin subtype 8 (TRPM8) is a nonselective, multimodal ion channel, activated by low temperatures (<28 °C), pressure, and cooling compounds (menthol, icilin). Experimental evidences indicated a role of TRPM8 in cold thermal transduction, different life-threatening tumors, and other pathologies, including migraine, urinary tract dysfunction, dry eye disease, and obesity. Hence, the modulation of the TRPM8 channel could be essential in order to understand its implications in these pathologies and for therapeutic intervention. This short review will cover recent progress on the TRPM8 agonists and antagonists, describing newly reported chemotypes, and their application in the pharmacological characterization of TRPM8 in health and disease. The recently described structures of the TRPM8 channel alone or complexed with known agonists and PIP2 are also discussed.

Keywords: TRPM8; agonists; antagonists; structure.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Natural products and recently described menthol-derived TRPM8 agonists.
Figure 2
Figure 2
Recently described non-menthol chemotypes acting as TRPM8 agonists.
Figure 3
Figure 3
Selective TRPM8 antagonists that have reached clinical trials.
Figure 4
Figure 4
Lately described TRPM8 antagonists.
Figure 5
Figure 5
Natural product-derived and marketed drug TRPM8 antagonists.
Figure 6
Figure 6
Partial structure of the TRPM8 (gray)/WS-12 (green) complex (generated from 6NR2, https://www.rcsb.org/structure/6NR2).
See this image and copyright information in PMC

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