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

Daniela Masciocchi, Stefania Villa, Fiorella Meneghetti, Alessandro Pedretti, Daniela Barlocco, Laura Legnani, Lucio Toma, Byoung Mog Kwon, Shintaro Nakano, Akira Asai, Arianna Gelain

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)592-599
Number of pages8
JournalMedChemComm
Volume3
Issue number5
DOIs
Publication statusPublished - May 2012

ASJC Scopus subject areas

  • Biochemistry
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Biological and computational evaluation of an oxadiazole derivative (MD77) as a new lead for direct STAT3 inhibitors'. Together they form a unique fingerprint.

Cite this