title: c-MET kinase inhibitors: a patent review (2011 - 2013).
abstract: BACKGROUND
  The receptor tyrosine kinase c-MET displays aberrant activation in the malignant phenotype of various tumors, and thus, has drawn considerable attention as drug target for cancer therapy. Many c-MET inhibitors are now under clinical investment, and one of them - Cabozantinib - has been approved by US FDA in 2012 for the treatment of medullary thyroid cancer, which further proved the feasibility of c-MET inhibition method in cancer therapy.
  
  
  METHODS
  This article briefly outlines the role of c-MET in oncogenesis and provides a broad overview of the assays used to characterize new inhibitors. Then, a series of representative small-molecule inhibitors of c-MET, especially from the published patent literature from 2011 to 2013, are recorded. Herein, the challenges in the kinase inhibitor design, such as the inhibitor selectivity and resistance mutations, are also discussed.
  
  
  CONCLUSIONS
  Up to now, at least 17 inhibitors of c-MET are under clinical evaluation, and several agents exhibit encouraging results. Thus, inhibiting c-MET signaling has major therapeutic value in cancer therapy. Focus on the selectivity of both types of inhibitors, with potent selectivity or multi-targets, have demonstrated antitumor efficacy. The network pharmacology and clinical trials integrated would provide powerful tools to further evaluate the superiority of both inhibitors in continued efficacy and toxicity.
authors.affiliation: Soochow University, Center for Systems Biology , Jiangsu 215006 , China +86 21 50271399 ; +86 21 50807088 ; zjliang@suda.edu.cn.
authors.forename: Kongkai
authors.initials: K
authors.lastname: Zhu
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Kong
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Liang
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D004335:Drug and Narcotic Control; D006801:Humans; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D010330:Patents as Topic; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met