Identification of a new STAT3 dimerization inhibitor through a pharmacophore-based virtual screening approach
Articolo
Data di Pubblicazione:
2016
Citazione:
Identification of a new STAT3 dimerization inhibitor through a pharmacophore-based virtual screening approach / G. Poli, A. Gelain, F. Porta, A. Asai, A. Martinelli, T. Tuccinardi. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - 31:6(2016 Dec), pp. 1011-1017.
Abstract:
Signal transducer and activator of transcription 3 (STAT3) plays an essential role in cell growth regulation and survival. An aberrant STAT3 activation and/or expression is implied in various solid and blood tumors as well as in other pathologies like rheumatoid arthritis and pulmonary fibrosis, thus making the search for STAT3 inhibitors a growing field of study. With the aim of identifying new inhibitors of STAT3 dimerization, we screened a database including more than 1 320 000 commercially available compounds using a receptor-based pharmacophore model comprising the key protein–protein interactions identified in the STAT3 dimer and refining the search through docking and molecular dynamic simulations studies. STAT3 binding assays revealed a significant STAT3 inhibitory activity and selectivity versus Grb2 for one of the four top-scored compounds, thus verifying the reliability of the virtual screening workflow. Moreover, such compound could already be considered as a lead for the development of new and more potent STAT3 dimerization inhibitors.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Docking; pharmacophore model; STAT3; virtual screening
Elenco autori:
G. Poli, A. Gelain, F. Porta, A. Asai, A. Martinelli, T. Tuccinardi
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