title: Tyrosine kinases as targets for cancer therapy.
abstract: Enhanced protein tyrosine kinase (PTK) activity correlates with the development of cancer and other proliferative diseases. The hypothesis that PTK inhibitors may be of value in the treatment of cancer led to the systematic synthesis of selective tyrosine phosphorylation inhibitors (tyrphostins) that show in vitro and in vivo anticancer activity. This review will provide an overview of research efforts in the development of tyrphostins such as AG 957, AG 1112, and AG 1318. Other tyrphostins discussed are AG 1478 and RG 13022, which are both epidermal growth factor receptor kinase inhibitors; AG 490, a Jak-2 kinase inhibitor; AG 1296, a PDGFR kinase inhibitor; and STI 571 (imatinib, Glivec/Gleevec; Novartis Pharma AG, Basel, Switzerland). STI 571 is now approved for the treatment of chronic myeloid leukemia and shows activity against gastrointestinal stromal tumors. The chemistry, kinetics, biological activity, and clinical potential of these compounds will be discussed.
authors.affiliation: Unit of Cellular Signaling, Department of Biological Chemistry, The Silverman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. levitzki@vms.huji.ac.il
authors.forename: Alexander
authors.initials: A
authors.lastname: Levitzki
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D020032:Tyrphostins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D020032:Tyrphostins; D011505:Protein-Tyrosine Kinases