Molecular pharmacology of the onco-TRP channel TRPV6

ABSTRACT

TRPV6, a representative of the vanilloid subfamily of TRP channels, serves as the principal calcium uptake channel in the gut. Dysregulation of TRPV6 results in disturbed calcium homeostasis leading to a variety of human diseases, including many forms of cancer. Inhibitors of this oncochannel are therefore particularly needed. In this review, we provide an overview of recent advances in structural pharmacology that uncovered the molecular mechanisms of TRPV6 inhibition by a variety of small molecules, including synthetic and natural, plant-derived compounds as well as some prospective and clinically approved drugs.

KEYWORDS:

• TRPV6
• TRP channels
• cancer
• inhibitor
• cryo-EM
• structural biology

Acknowledgments

The authors thank Jeffrey Khau and Kirill D. Nadezhdin for comments. A.N. is a Walter Benjamin Fellow funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)–464295817. A.I.S. was supported by the NIH (R01 AR078814, R01 CA206573, R01 NS083660, R01 NS107253).

Disclosure statement

The authors declare the absence of any conflicts of interest.

Author contributions

A.N. and A.I.S wrote the manuscript.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

The work was supported by the Deutsche Forschungsgemeinschaft [464295817]; National Cancer Institute [CA206573]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR078814]; National Institute of Neurological Disorders and Stroke [NS083660]; National Institute of Neurological Disorders and Stroke [NS107253].