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Rodrigues, Tiago; Werner, Markus; Roth, Jakob; da Cruz, Eduardo H G; Marques, Marta C; Akkapeddi, Padma; Lobo, Susana A; Koeberle, Andreas; Corzana, Francisco; da Silva Júnior, Eufrânio N; Werz, Oliver; Bernardes, Gonçalo J L
Chemical science, 2018, Letnik: 9, Številka: 34Journal Article
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.
