title: Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors.
abstract: Inhibition of the signaling pathways of signal transducer and activator of transcription 3 (STAT 3) has shown to be a promising strategy to combat cancer. In this paper we report the design, synthesis and evaluation of a novel class of small molecule inhibitors, that is, XZH-5 and its analogues, as promising leads for further development of STAT3 inhibitors. Preliminary SARs was established for XZH-5 and its derivatives; and the binding modes were predicted by molecular docking. Lead compounds with IC50 as low as 6.5μM in breast cancer cell lines and 7.6μM in pancreatic cancer cell lines were identified.
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA.
authors.forename: Philias
authors.initials: P
authors.lastname: Daka
authors.affiliation: Department of Pediatrics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430030, PR China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA.
authors.forename: Chamini
authors.initials: C
authors.lastname: Karunaratne
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Csatary
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA.
authors.forename: Cameron
authors.initials: C
authors.lastname: Williams
authors.affiliation: Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, The Ohio State University, Columbus, OH, USA; Molecular, Cellular and Developmental Biology Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, The Ohio State University, Columbus, OH, USA; Molecular, Cellular and Developmental Biology Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Jiayuh
authors.initials: J
authors.lastname: Lin
authors.affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, PR China.
authors.forename: Zhenghu
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA. Electronic address: pagerc@miamioh.edu.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Page
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA. Electronic address: wangh3@miamioh.edu.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006639:Histidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D010671:Phenylurea Compounds; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C560270:XZH-5 compound; D006639:Histidine
keywords: Inhibitor; Molecular docking; SARs; SH2; STAT3; Small organic molecule