Machine intelligence decrypts β-lapachone as an allosteric 5-lipoxygenase inhibitor.
Published version
Peer-reviewed
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Repository DOI
Change log
Authors
Rodrigues, Tiago https://orcid.org/0000-0002-1581-5654
Werner, Markus
Roth, Jakob
da Cruz, Eduardo HG
Marques, Marta C
Abstract
Using machine learning, targets were identified for β-lapachone. Resorting to biochemical assays, β-lapachone was validated as a potent, ligand efficient, allosteric and reversible modulator of 5-lipoxygenase (5-LO). Moreover, we provide a rationale for 5-LO modulation and show that inhibition of 5-LO is relevant for the anticancer activity of β-lapachone. This work demonstrates the power of machine intelligence to deconvolute complex phenotypes, as an alternative and/or complement to chemoproteomics and as a viable general approach for systems pharmacology studies.
Description
Keywords
0801 Artificial Intelligence and Image Processing
Journal Title
Chem Sci
Conference Name
Journal ISSN
2041-6520
2041-6539
2041-6539
Volume Title
9
Publisher
Royal Society of Chemistry (RSC)
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Sponsorship
European Research Council (676832)
Royal Society (URF\R\180019)
Engineering and Physical Sciences Research Council (EP/M003647/1)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (675007)
European Commission (EC) (852985)
Royal Society (URF\R\180019)
Engineering and Physical Sciences Research Council (EP/M003647/1)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (675007)
European Commission (EC) (852985)