title: Type II kinase inhibitors: an opportunity in cancer for rational design.
abstract: With the advent of the Type II kinase inhibitor imatinib (Gleevec) for treatment against cancer, rational design of tailored molecules has brought a revolution in medicinal chemistry for treating tumours caused by kinase malfunctioning. Among different types of kinase inhibitors, the design of Type II inhibitors has been rationalized for maximizing the benefits and reducing drawbacks. Here we highlight the development made in Type II inhibitors, discussing the advantages and disadvantages of these types of molecules. Furthermore, we present the strategies for designing druggable molecules that either selectively inhibit target kinases or overcome drug resistance.
authors.affiliation: Department of Medicinal Chemistry, Galápagos NV, Mechelen, Belgium. javier.blanc@glpg.com
authors.forename: Javier
authors.initials: J
authors.lastname: Blanc
authors.forename: Raphaël
authors.initials: R
authors.lastname: Geney
authors.forename: Christel
authors.initials: C
authors.lastname: Menet
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D000068877:Imatinib Mesylate; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000145:classification / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate