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Issue 5, 2012
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Biological and computational evaluation of an oxadiazole derivative (MD77) as a new lead for direct STAT3 inhibitors

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Abstract

Signal Transducer and Activator of Transcription 3 (STAT3) is a latent cytoplasmic protein overexpressed in various cancer cell lines. STAT3 participates in oncogenesis by stimulating cell proliferation and preventing apoptosis and it has been proven as a suitable target for anticancer therapy. In order to identify direct STAT3 inhibitors, we performed a binding assay on several previously synthesized 1,2,5-oxadiazole derivatives. Among them, compound MD77, N-[4-(4-chlorophenyl)-1,2,5-oxadiazol-3-yl]-4-(trifluoromethyl)benzamide, showed a good ability to bind the STAT3–SH2 domain in a dose-dependent manner (IC50 = 17.7 μM). Computational studies were carried out to investigate its binding mode. Moreover, compound MD77 showed a significant anti-proliferative activity versus several tumor cell lines. On these bases, compound MD77 was selected as a lead for the future development of direct STAT3 inhibitors.

Graphical abstract: Biological and computational evaluation of an oxadiazole derivative (MD77) as a new lead for direct STAT3 inhibitors

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Publication details

The article was received on 25 Jan 2012, accepted on 27 Feb 2012 and first published on 26 Mar 2012


Article type: Concise Article
DOI: 10.1039/C2MD20018J
Med. Chem. Commun., 2012,3, 592-599

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    Biological and computational evaluation of an oxadiazole derivative (MD77) as a new lead for direct STAT3 inhibitors

    D. Masciocchi, S. Villa, F. Meneghetti, A. Pedretti, D. Barlocco, L. Legnani, L. Toma, B. Kwon, S. Nakano, A. Asai and A. Gelain, Med. Chem. Commun., 2012, 3, 592
    DOI: 10.1039/C2MD20018J

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