Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents.
Chemical Society Reviews
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Rodrigues, T., Sieglitz, F., & Lopes Bernardes, G. (2016). Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents.. Chemical Society Reviews, 45 (22), 6130-6137. https://doi.org/10.1039/c5cs00916b
Treatment of cancer is a significant challenge in clinical medicine, and its research is a top priority in chemical biology and drug discovery. Consequently, there is an urgent need for identifying innovative chemotypes capable of modulating unexploited drug targets. The transient receptor potential (TRPs) channels persist scarcely explored as targets, despite intervening in a plethora of pathophysiological events in numerous diseases, including cancer. Both agonists and antagonists have proven capable of evoking phenotype changes leading to either cell death or reduced cell migration. Among these, natural products entail biologically pre-validated and privileged architectures for TRP recognition. Furthermore, several natural products have significantly contributed to our current knowledge on TRP biology. In this Tutorial Review we focus on selected natural products, e.g. capsaicinoids, cannabinoids and terpenes, by highlighting challenges and opportunities in their use as starting points for designing natural product-inspired TRP channel modulators. Importantly, the de-orphanization of natural products as TRP channel ligands may leverage their exploration as viable strategy for developing anticancer therapies. Finally, we foresee that TRP channels may be explored for the selective pharmacodelivery of cytotoxic payloads to diseased tissues, providing an innovative platform in chemical biology and molecular medicine.
Antineoplastic Agents, Biological Products, Cell Death, Humans, Neoplasms, Transient Receptor Potential Channels
We thank FCT Portugal (FCT Investigator to G. J. L. B.), the EU (Marie-Curie CIG and Marie-Curie ITN Protein Conjugates to G. J. L. B.), Deutsche Forschungsgemeinschaft (Postdoctoral Fellowship to F. S.), the EPSRC and MRC for funding. G. J. L. B. is a Royal Society University Research Fellow and the recipient of an European Research Council Starting Grant (TagIt).
External DOI: https://doi.org/10.1039/c5cs00916b
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253811
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/