title: The molecular mechanisms of a novel multi-kinase inhibitor ZLJ33 in suppressing pancreatic cancer growth.
abstract: ZLJ33, an oral active multi-kinase inhibitor, was evaluated both in vitro and in vivo against human pancreatic cancer. It could effectively inhibit cell proliferation, induce apoptosis, and cause inhibition of invasion in pancreatic cancer cells. At a dose of 15.0 mg/kg, ZLJ33 induced tumor shrink in Mia-PaCa2, Capan2, and AsPC-1 xenografts models by 60.59%, 74.19%, and 71.54% according to the tumor weight, respectively. The effect of ZLJ33 on pancreatic cancer was mainly mediated by inactivation of p-PDGFRβ, p-c-Raf, and p-RET. Treatment with ZLJ33 did not cause side effect of hematology indexes in the pancreatic cancer xenograft model. ZLJ33 could be a potential therapeutic agent against pancreatic cancer.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Department of Pharmacochemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Wanqi
authors.initials: W
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Hanze
authors.initials: H
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Department of Pharmacochemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: fengzhq@imm.ac.cn.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: chxg@imm.ac.cn.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D000077157:Sorafenib; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D051176:beta Catenin / Q000378:metabolism
chemical_list: D006834:Hydrazines; D010671:Phenylurea Compounds; D018809:Proliferating Cell Nuclear Antigen; D047428:Protein Kinase Inhibitors; C000595659:ZLJ33 compound; D051176:beta Catenin; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Antiproliferation; Multi-kinase inhibitor; PDGFRβ; Pancreatic cancer; RET; c-Raf