title: The salicylanilide derivatives inhibit signal transducer and activator of transcription 3 pathways in A549 lung cancer cells.
abstract: The signal transducer and activator of transcription 3 (STAT3) is constitutively activated in certain cancer cells. Therefore, blocking the aberrant activity of STAT3 in tumor cells is a validated therapeutic strategy. To discover novel inhibitors of STAT3 activity, we report the salicylanilide derivatives as a new small molecule inhibitor of the STAT3 signaling pathway. The N-(3-chloro-4-fluorophenyl)-2-hydroxy-4-(3-(piperidin-1-yl)propoxy) benzamide potently inhibited the activation and transcriptional function of STAT3. These studies further validate STAT3 as a drug discovery target and provide evidence that pharmacological agents that can selectively reduce the phospho-STAT3 levels in human cancer cells result in tumor apoptosis and growth inhibition.
authors.affiliation: aDepartment of Pharmaceutical Chemistry, Anhui University of Chinese Medicine bHefei Medical Engineering Pharmaceutical Co. Ltd, Hefei, People's Republic of China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Hu
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Ye
authors.forename: Jiaming
authors.initials: J
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.forename: Zhaoxin
authors.initials: Z
authors.lastname: Chu
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000813:Anilides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012457:Salicylamides / Q000494:pharmacology*; D012458:Salicylanilides / Q000494:pharmacology*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: C000602517:4-(3-(piperidin-1-yl)propoxy)-N-(3-chloro-4-fluorophenyl)-2-hydroxybenzamide; D000813:Anilides; D000970:Antineoplastic Agents; D001549:Benzamides; C000607984:N-(3-chloro-4-fluorophenyl)-2-hydroxy-4-(3-morpholinopropoxy)benzamide; D010880:Piperidines; D050796:STAT3 Transcription Factor; D012457:Salicylamides; D012458:Salicylanilides; D019000:Phosphotyrosine; C507924:JAK2 protein, human; D053614:Janus Kinase 2