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.

Masciocchi, D., Villa, S., Meneghetti, F., Pedretti, A., Barlocco, D., Legnani, L., et al. (2012). Biological and computational evaluation of an oxadiazole derivative (MD77) as a new lead for direct STAT3 inhibitors. MEDCHEMCOMM, 3(5), 592-599 [10.1039/c2md20018j].

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

Legnani, L;
2012

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.
Articolo in rivista - Articolo scientifico
Molecular modeling; Antitumor activity; Oxadiazoles;
English
592
599
8
Masciocchi, D., Villa, S., Meneghetti, F., Pedretti, A., Barlocco, D., Legnani, L., et al. (2012). Biological and computational evaluation of an oxadiazole derivative (MD77) as a new lead for direct STAT3 inhibitors. MEDCHEMCOMM, 3(5), 592-599 [10.1039/c2md20018j].
Masciocchi, D; Villa, S; Meneghetti, F; Pedretti, A; Barlocco, D; Legnani, L; Toma, L; Kwon, B; Nakano, S; Asai, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/351952
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