Issue 34, 2018

Machine intelligence decrypts β-lapachone as an allosteric 5-lipoxygenase inhibitor

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.

Graphical abstract: Machine intelligence decrypts β-lapachone as an allosteric 5-lipoxygenase inhibitor

Supplementary files

Article information

Article type
Edge Article
Submitted
14 iyn 2018
Accepted
17 iyl 2018
First published
17 iyl 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2018,9, 6899-6903

Machine intelligence decrypts β-lapachone as an allosteric 5-lipoxygenase inhibitor

T. Rodrigues, M. Werner, J. Roth, E. H. G. da Cruz, M. C. Marques, P. Akkapeddi, S. A. Lobo, A. Koeberle, F. Corzana, E. N. da Silva Júnior, O. Werz and G. J. L. Bernardes, Chem. Sci., 2018, 9, 6899 DOI: 10.1039/C8SC02634C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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