Therapeutic protein kinase inhibitors.
Protein kinase inhibitors represent an important and still emerging class of targeted therapeutic agents. Drug discovery and development strategies have explored numerous approaches to target the inhibition of protein kinase signaling. This review will highlight some of the strategies that have led to the successful clinical development of therapeutic protein kinase inhibitors, particularly as anticancer drugs. Some notable advances have been made in the development of novel protein and oligonucleotide-based biologics that target growth factor or receptor tyrosine kinases. Also, advances have been made in the rational design of small-molecule inhibitors that target unique kinase conformational forms and binding sites, and have specific kinase selectivity profiles. A review will also be given of some of the potential clinical toxicities and adverse side-effects associated with these kinase-targeted drugs. Therapeutic protein kinase inhibitors have been highly beneficial to cancer patients and offer the promise of future therapies for other diseases as well.
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Department of Biochemical Pharmacology, Pfizer Global Research & Development, Pfizer La Jolla Laboratories, 10777 Science Center Drive, San Diego, CA 92121, USA. stephan.grant@pfizer.com
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D020794:Receptor Protein-Tyrosine Kinases