title: Novel anticancer targets and drug discovery in post genomic age.
abstract: Cancer is a serious disease with a complex pathogenesis, which threats human life greatly. Currently, great efforts have been put to the identification of novel anticancer targets and the discovery of anticancer drugs following the progress of chemogenomics, which will be reviewed briefly in this article. Furthermore, during the past 5 years, the global effort of sequencing human genome has provided us with an enormous number of potential targets associated with cancer therapy. As a result, the New Drug Discovery (NDD) is undergoing a transition "from gene to drug". Accordingly, the targets for anticancer drugs studies now are focused on some biological macromolecular targets associated with cancer and several interactive mechanisms involved in the growth and metastasis of cancer cells as well as tumor angiogenesis, such as Matrix Metalloproteinases (MMPs), Aminopeptidase N (APN), Tyrosine Kinase (TK), Farnesyltransferase (FTase) and cell Signal Transduction Pathway and so forth. Among these targets the MMP-2, -9 and APN are the most extensively studied enzymes in our laboratory. The peptidomimetics Matrix Metalloproteinase Inhibitors (MMPIs) and APN inhibitors (APNIs) with the molecular scaffold of pyrrolidine, 3-amino-2-hydroxy-4-phenyl butyric acid (AHPA) and glutamylide, which have been designed and synthesized in our laboratory, will be described in the review, among which the pyrrolidine scaffold is patented with the IC(50) ranging from 1 nM to 300 nM against MMP-2, and MMP-9.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, ShanDong University, 44 West Culture Road, 250012, Ji'nan, ShanDong, P.R.China. drqbli@yahoo.com.cn
authors.forename: Qianbin
authors.initials: Q
authors.lastname: Li
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000187:drug effects; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents; D018826:CD13 Antigens / Q000187:drug effects; D051546:Cyclooxygenase 2; D015195:Drug Design; D051231:Farnesyltranstransferase; D023281:Genomics; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects; D006655:Histone Deacetylases / Q000187:drug effects; D016023:Integrins / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects; D017466:Receptors, Endothelin / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D016023:Integrins; D017466:Receptors, Endothelin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D011505:Protein-Tyrosine Kinases; D018826:CD13 Antigens; D020782:Matrix Metalloproteinases; D006655:Histone Deacetylases