Novel oncogenic protein kinase inhibitors for cancer therapy.
Small-molecule drug discovery for cancer therapy is making extraordinary progress within the realm of advancing novel oncogenic protein kinase inhibitor lead compounds of significant impact to both basic research and clinical testing. In this perspective, structure- and mechanism-based drug design are highlighted relative to such progress. Also, evolving concepts in novel oncogenic protein kinase inhibitor drug discovery is highlighted relative to therapeutic target selectivity, including the recent identification of oncogenic kinase mutants effecting drug-resistance or enhanced drug susceptibility to small-molecule inhibitors.
Sawyer
Tomi K
TK
ARIAD Pharmaceuticals, Inc., 26 Landsdowne St., Cambridge, MA 01772, USA. tomi.sawyer@ariad.com
D000255:Adenosine Triphosphate / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019992:Databases as Topic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008956:Models, Chemical; D011494:Protein Kinases / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013997:Time Factors; D014965:X-Rays
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases