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dc.contributor.authorCampa, Carlo C.-
dc.contributor.authorSilva, Rangel L.-
dc.contributor.authorMargaria, Jean P.-
dc.contributor.authorPiral, Tracey-
dc.contributor.authorMattos, Matheus S.-
dc.contributor.authorKraemer, Lucas R.-
dc.contributor.authorReis, Diego C.-
dc.contributor.authorGrosa, Giorgio-
dc.contributor.authorCopperi, Francesca-
dc.contributor.authorDalmarco, Eduardo M.-
dc.contributor.authorLima-Júnior, Roberto C.P.-
dc.contributor.authorAprile, Silvio-
dc.contributor.authorSala, Valentina-
dc.contributor.authorBello, Bello-
dc.contributor.authorPrado, Douglas Silva-
dc.contributor.authorAlves-Filho, Jose Carlos-
dc.contributor.authorMedana, Claudio-
dc.contributor.authorCassali, Geovanni D.-
dc.contributor.authorTron, Gian Cesare-
dc.contributor.authorTeixeira, Mauro M.-
dc.contributor.authorCiraolo, Elisa-
dc.contributor.authorRusso, Remo C.-
dc.contributor.authorHirsch, Emilio-
dc.identifier.citationCAMPA, Carlo C. et al. Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis. Nature Communications, v. 12, n. 5232, p. 1-16, dec. 2018.pt_BR
dc.description.abstractPI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis.pt_BR
dc.publisherNature Communicationspt_BR
dc.titleInhalation of the prodrug PI3K inhibitor CL27cimproves lung function in asthma andfibrosispt_BR
dc.typeArtigo de Periódicopt_BR
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