title: Recently targeted kinases and their inhibitors-the path to clinical trials.
abstract: Protein kinases have emerged as one of the most important drug target families for the treatment of cancer. To date, 28 inhibitors with reported activity versus one or multiple kinases have been approved for clinical use. However, the majority of new clinical trials are focused on new subindications using already approved kinase inhibitors or target well validated kinase targets with novel inhibitors. In contrast, relatively few clinical trials have been initiated using specific inhibitors that inhibit novel kinase targets, despite significant validation efforts in the public domain. Analysis of the target validation history of first in class kinase inhibitors revealed a long delay between initial disease association and development of inhibitors. As part of this analysis, we have investigated which first in class inhibitor that entered phase I clinical trials over the last five years and also considered which research approaches that were used to validate them.
authors.affiliation: Nuffield Department of Clinical Medicine, Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Knapp
authors.affiliation: Department of Medicine, Karolinska University Hospital and Karolinska Institutet, 171 76 Stockholm, Sweden. Electronic address: michael.sundstrom@ki.se.
authors.forename: Michael
authors.initials: M
authors.lastname: Sundström
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D057170:Translational Research, Biomedical
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors