xzh-5 inhibits stat3 phosphorylation and enhances the cytotoxicity of chemotherapeutic drugs in human breast and pancreatic cancer cellsxzh-5抑制stat3磷酸化和增强细胞毒性化疗药物在人类乳腺癌和胰腺癌细胞.pdfVIP

XZH-5 Inhibits STAT3 Phosphorylation and Enhances the Cytotoxicity of Chemotherapeutic Drugs in Human Breast and Pancreatic Cancer Cells 1,2 2¤ 4 1 2,5 2 4 6 Aiguo Liu *, Yan Liu , Zhigang Jin , Qun Hu , Li Lin , David Jou , Jing Yang , Zhenghu Xu , 6 7 2,3 Hong Wang , Chenglong Li , Jiayuh Lin * 1 Department of Pediatrics, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China, 2 Center for Childhood Cancer, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States of America, 3 Molecular, Cellular and Developmental Biology Program, The Ohio State University, Columbus, Ohio, United States of America, 4 Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana- Champaign, Urbana, Illinois, United States of America, 5 Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China, 6 Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, United States of America, 7 Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, United States of America Abstract Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) signaling is frequently detected in breast and pancreatic cancer. Inhibiting constitutive STAT3 signaling represents a promising molecular target for therapeutic approach. Using structure-based design, we developed a non-peptide cell-permeable, small molecule, termed as XZH-5, which targeted STAT3 phosphor