title: FDA-approved small-molecule kinase inhibitors.
abstract: Kinases have emerged as one of the most intensively pursued targets in current pharmacological research, especially for cancer, due to their critical roles in cellular signaling. To date, the US FDA has approved 28 small-molecule kinase inhibitors, half of which were approved in the past 3 years. While the clinical data of these approved molecules are widely presented and structure-activity relationship (SAR) has been reported for individual molecules, an updated review that analyzes all approved molecules and summarizes current achievements and trends in the field has yet to be found. Here we present all approved small-molecule kinase inhibitors with an emphasis on binding mechanism and structural features, summarize current challenges, and discuss future directions in this field.
authors.affiliation: Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark. Electronic address: penwu@kemi.dtu.dk.
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.affiliation: Protein and Peptide Chemistry, Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Nielsen
authors.affiliation: Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark; Center for Nanomedicine and Theranostics, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Mads H
authors.initials: MH
authors.lastname: Clausen
mesh_terms: D017277:Drug Approval; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010770:Phosphotransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010770:Phosphotransferases; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases
keywords: cancer; crystal structure; lipid kinase; protein kinase; serine/threonine kinase; tyrosine kinase