Targeting and extending the eukaryotic druggable genome with natural products: cytoskeletal targets of natural products

Covering: 2014-2019 We review recent progress on natural products that target cytoskeletal components, including microtubules, actin, intermediate filaments, and septins and highlight their demonstrated and potential utility in the treatment of human disease. The anticancer efficacy of microtubule t...

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Bibliographic Details
Published in:Natural product reports 2020-05, Vol.37 (5), p.634-652
Main Authors: Risinger, April L, Du, Lin
Format: Article
Language:English
Subjects:
Actin
Anticancer properties
Cancer
Cytoskeleton
DNA probes
Drug resistance
Filaments
Genomes
Health services
Infectious diseases
Intermediate filaments
Marine organisms
Marine plants
Medical treatment
Microtubules
Natural products
Neurological diseases
Probes
Toxins
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Summary:Covering: 2014-2019 We review recent progress on natural products that target cytoskeletal components, including microtubules, actin, intermediate filaments, and septins and highlight their demonstrated and potential utility in the treatment of human disease. The anticancer efficacy of microtubule targeted agents identified from plants, microbes, and marine organisms is well documented. We highlight new microtubule targeted agents currently in clinical evaluations for the treatment of drug resistant cancers and the accumulating evidence that the anticancer efficacy of these agents is not solely due to their antimitotic effects. Indeed, the effects of microtubule targeted agents on interphase microtubules are leading to their potential for more mechanistically guided use in cancers as well as neurological disease. The discussion of these agents as more targeted drugs also prompts a reevaluation of our thinking about natural products that target other components of the cytoskeleton. For instance, actin active natural products are largely considered chemical probes and non-selective toxins. However, studies utilizing these probes have uncovered aspects of actin biology that can be more specifically targeted to potentially treat cancer, neurological disorders, and infectious disease. Compounds that target intermediate filaments and septins are understudied, but their continued discovery and mechanistic evaluations have implications for numerous therapeutic indications. This review describes natural products that target the cytoskeleton, including microtubules, actin, intermediate filaments, and septins, highlighting their utility for the treatment of human disease.
ISSN:0265-0568
1460-4752
DOI:10.1039/c9np00053d