title: SOMCL-863, a novel, selective and orally bioavailable small-molecule c-Met inhibitor, exhibits antitumor activity both in vitro and in vivo.
abstract: Deregulation of HGF/c-Met signaling and its driven neoplastic phenotype are associated with a variety of human malignancies. We herein reported SOMCL-863 as a novel selective c-Met inhibitor which effectively abrogated c-Met signaling pathways, thereby leading to substantial impairment of c-Met-dependent cell proliferation, migration, invasion, cell scattering and invasive growth. In EBC-1 and NCI-H1993 xenografts, SOMCL-863 exerted significant anti-tumor efficacy through anti-proliferative effects and antiangiogenic mechanisms, including reduction of tumor cell proliferation and reductions of microvessel density and secretion of proangiogenic factor IL-8. Together with the optimal pharmacokinetic properties, SOMCL-863 is a promising candidate worthy for further evaluation as a treatment of c-Met-driven human cancers.
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ai
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Haotian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Peng
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: CAS Key Laboratory of Receptor Research, and Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Ao
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: jding@simm.ac.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: mygeng@simm.ac.cn.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D045744:Cell Line, Tumor; D005260:Female; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011804:Quinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015398:Signal Transduction; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C066855:HGF protein, human; D011804:Quinolines; C000591276:SOMCL-863; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: Angiogenesis; Cancer; Receptor tyrosine kinase; SOMCL-863; c-Met