title: Identification and characterization of small molecule inhibitors of signal transducer and activator of transcription 3 (STAT3) signaling pathway by virtual screening.
abstract: Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway has been considered a novel therapeutic strategy to treat human cancers that harbor aberrantly-active STAT3. In this study, a series of small molecules were identified as novel inhibitors of STAT3 signaling pathway through virtual screening. A tricyclic scaffold containing compound, 6, was identified as an inhibitor of IL-6/STAT3 signaling with an IC50 of 26.68 μM. In addition, this compound inhibited Tyr705 phosphorylation of STAT3 and had no obvious effect on upstream tyrosine kinases. Thus, compound 6 is a potential lead structure and valuable for further drug development.
authors: School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors: Mingming
authors: M
authors: Zhang
authors: Weiliang
authors: W
authors: Zhu
authors: Ning
authors: N
authors: Ding
authors: Wei
authors: W
authors: Zhang
authors: Yingxia
authors: Y
authors: Li
mesh_terms: D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D054852:Small Molecule Libraries