TY - JOUR
T1 - Biological and computational evaluation of an oxadiazole derivative (MD77) as a new lead for direct STAT3 inhibitors
AU - Masciocchi, Daniela
AU - Villa, Stefania
AU - Meneghetti, Fiorella
AU - Pedretti, Alessandro
AU - Barlocco, Daniela
AU - Legnani, Laura
AU - Toma, Lucio
AU - Kwon, Byoung Mog
AU - Nakano, Shintaro
AU - Asai, Akira
AU - Gelain, Arianna
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
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U2 - 10.1039/c2md20018j
DO - 10.1039/c2md20018j
M3 - Article
AN - SCOPUS:84860438737
SN - 2040-2503
VL - 3
SP - 592
EP - 599
JO - MedChemComm
JF - MedChemComm
IS - 5
ER -