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

Abstract:

:Covering: 2014-2019We 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.

journal_name

Nat Prod Rep

journal_title

Natural product reports

authors

Risinger AL,Du L

doi

10.1039/c9np00053d

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

634-652

issue

5

eissn

0265-0568

issn

1460-4752

journal_volume

37

pub_type

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