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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Non-Photoinduced Biological Properties of Verteporfin

Author(s): Floriane Gibault, Matthieu Corvaisier, Fabrice Bailly, Guillemette Huet, Patricia Melnyk and Philippe Cotelle

Volume 23, Issue 11, 2016

Page: [1171 - 1184] Pages: 14

DOI: 10.2174/0929867323666160316125048

Price: $65


Background: Verteporfin is a porphyrinic photosensitizer clinically used for the photodynamic treatment of age-related macular degeneration. It has been identified almost simultaneously as a YAP/TEAD and an autophagosome inhibitor. Over the last few years, YAP (TAZ), the downstream effectors of the Hippo pathway, have emerged as promising anticancer targets, as shown by several experimental lines of evidence, showing the overproduction of YAP in several cancers. However, YAP was also found to be closely connected to autophagy, mitochondria and reactive oxygen/nitrogen species. We herein, review the recent studies where VP was used without photoactivation as a YAP/TEAD inhibitor or protein oligomerization promoter, focusing on its effects on the YAP/TEAD gene targets and other biomarkers related to autophagy. Results: Since the identification of VP as YAP/TEAD inhibitor, several in vitro and in vivo studies have revealed the new potential of this molecule in different cancers, where YAP is overexpressed. However, detailed structural information about its interaction with YAP is still lacking. Concomitantly, VP was identified as autophagosome inhibitor by promoting oligomerization of p62. Moreover, VP proves to be tumor-selective proteotoxic (by oligomerization of p62, STAT3) in colorectal cancer. Knowledge on the biological properties of the only YAP inhibitor available to date is vital for its pharmacological use on cellular and animal models. Conclusion: VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD.

Keywords: Hippo pathway, YAP/TEAD complex, non-photoinduced therapy, oncogene, autophagy, proteotoxicity.

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