title: Targeting the DFG-in kinase conformation: a new trend emerging from a patent analysis.
abstract: Aberrant kinase signaling leads to a multitude of disease states. The clinical and commercial success of agents typified by imatinib or dasatinib in the treatment of hematological malignancies has further validated kinase inhibition as a useful clinical strategy. This increased interest in kinases as therapeutic targets is evidenced by the rapidly increasing number of patent applications and peer-reviewed articles. This article discusses recent Patent that describe small molecules targeting the DFG-in active kinase conformation, by the so-called 'Type I½' inhibitor, against a small set of clinically relevant targets such as B-Raf, p38α, Jak2 and EphB4. Preclinical and clinical data are also highlighted for the most promising new molecular entities.
authors: Medicinal Chemistry Department, Oncology Business Unit, Nerviano Medical Sciences, 20014 Nerviano, Italy. mauro.angiolini@nervianoms.com
authors: Mauro
authors: M
authors: Angiolini
mesh_terms: D001549:Benzamides; D000069439:Dasatinib; D055808:Drug Discovery / Q000379:methods*; D000068877:Imatinib Mesylate; D007249:Inflammation / Q000188:drug therapy; D008958:Models, Molecular; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy; D010330:Patents as Topic; D010770:Phosphotransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010879:Piperazines; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D011743:Pyrimidines; D015398:Signal Transduction / Q000187:drug effects*; D013844:Thiazoles
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D010770:Phosphotransferases; D000069439:Dasatinib