Platelet-derived growth factor receptor tyrosine kinase inhibitors: a review of the recent patent literature.
BACKGROUND
Platelet-derived growth factor receptor (PDGFR) is a compelling target for developing therapeutic agents to treat diseases associated with overactivated platelet-derived growth factor (PDGF) signaling and has proved to be particularly encouraging for cancer treatment. The efforts in this area have been greatly enhanced by the approval of tyrosine kinase inhibitors with PDGFR inhibitory activity such as imatinib, sunitinib and sorafenib.


METHODS
This review surveys the small molecule PDGFR inhibitors reported in patent literature over the past 5 years (2005 - 2009).


RESULTS
The reader will gain an overview of the chemical scaffolds and the activity/selectivity of the newly discovered PDGFR inhibitors.


CONCLUSIONS
Targeting PDGFR kinase with small molecule inhibitors has remained a very active area. Many new and novel PDGFR inhibitors with different selectivity profiles are being discovered and evaluated. In cancer therapy, the identification of novel and potent PDGFR inhibitors with preferred kinase inhibitory profiles that deliver superior antitumor efficacy, yet have manageable side effects and toxicities, will continue to be the key for success. Additionally, interest in targeting PDGF signaling for intervention of various vascular diseases and fibrotic conditions is expected to continue to grow.
Cancer Research, Abbott Laboratories, Department R47J, Building AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA. yujia.dai@abbott.com
Yujia
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Dai
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D017479:Receptors, Platelet-Derived Growth Factor