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Mining Natural Compounds to Target WNT Signaling: Land and Sea Tales

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Pharmacology of the WNT Signaling System

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 269))

Abstract

WNT signaling plays paramount roles in organism development, physiology, and disease, representing a highly attractive target for drug development. However, no WNT-modulating drugs have been approved, with several candidates trudging through the early clinical trials. This delay instigates alternative approaches to discover WNT-modulating drugs. Natural products were the source of therapeutics for centuries, but the chemical diversity they offer, especially when looking at different taxonomic groups and habitats, is still to a large extent unexplored. These considerations urge researchers to screen natural compounds for the WNT-modulatory activities. Since several reviews on such endeavors exist, we here have attempted to present these efforts as “Land and sea tales” (citing the book title by Rudyard Kipling) superimposing them onto the traditional pipeline of drug discovery and early development. In doing so, we illustrate each step of the pipeline with case studies stemming from our own research. It will become obvious that several steps of the pipeline need to be modified when applied to natural products rather than to synthetic libraries. Yet the main message of this chapter is that natural compounds represent a powerful source for the WNT signaling modulators and can be developed towards drug candidates against WNT-dependent maladies.

“Land and sea tales” is a book by Rudyard Kipling.

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Acknowledgements

The deep-sea and marine investigations described in this chapter were funded by the Ministry of Science and Higher Education of Russian Federation (grant 13.1902.21.0012 “Fundamental problems of investigation and preservation of deep-sea ecosystems of potentially ore-bearing regions of the Northwestern Pacific,” contract No. 075-15-2020-796).

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Authors and Affiliations

  1. Department of Cell Physiology and Metabolism, Faculty of Medicine, Translational Research Centre in Oncohaematology, University of Geneva, Geneva, Switzerland

    Vladimir L. Katanaev, Jiabin Xu & Alexey Koval

  2. School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia

    Vladimir L. Katanaev, Artem Blagodatski & Yuri Khotimchenko

  3. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences Pushchino, Moscow, Russia

    Artem Blagodatski

  4. National Scientific Center for Marine Biology, Far Eastern Branch of Russian Academy of Sciences, Vladivostok, Russia

    Yuri Khotimchenko

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  1. Vladimir L. Katanaev
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  2. Artem Blagodatski
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  3. Jiabin Xu
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  4. Yuri Khotimchenko
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  5. Alexey Koval
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Correspondence to Vladimir L. Katanaev .

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  1. Department of Physiology & Pharmacology Section for Receptor Biology & Signaling, Karolinska Institutet Biomedicum 6D, Stockholm, Sweden

    Gunnar Schulte

  2. Department of Physiology & Pharmacology Section for Receptor Biology & Signaling, Karolinska Institutet Biomedicum 6D, Stockholm, Sweden

    Pawel Kozielewicz

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Katanaev, V.L., Blagodatski, A., Xu, J., Khotimchenko, Y., Koval, A. (2021). Mining Natural Compounds to Target WNT Signaling: Land and Sea Tales. In: Schulte, G., Kozielewicz, P. (eds) Pharmacology of the WNT Signaling System. Handbook of Experimental Pharmacology, vol 269. Springer, Cham. https://doi.org/10.1007/164_2021_530

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