Protein kinase inhibitors, for cancer

Dancey J, Sausville EA (2003) Issues and progress with protein kinase inhibitors for cancer treatment. Nat. Rev. Drug Discov. 2 296-313... 

Daidzein and genistein have been most intensively investigated because of their high levels of occurrence in soybean, a widely used animal feedstuff and a component of traditional Asian diets consumed daily in high quantities by Japanese [10] and Chinese populations [8, 11]. The consumption of products derived from soy has, therefore, been considered as the major dietary factor contributing to the lower rates of hormone-dependent diseases, including breast, prostate, and colon cancers and coronary heart disease, in many Asian countries [12-14]. Almost 10 years after Akiyama et al. [15] first identified genistein as a tyrosine protein kinase inhibitor [15], it was entered into clinical chemoprevention trials in 1996 [16, 17], followed by formal human trials as a treatment for acute lymphoblastic leukemia and breast cancer [18-20]. 

AstraZeneca s gefitinib (Iressa) s core structure is a quinazoline. It is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) indicated for the treatment of cancers. Several other protein kinase inhibitors also used the quinazoline ring as their core structure. They include OSI s erlotinib (Tarceva) and GSK s lapatinib (Tykerb). 

Lawrence, D. S. Fluorescent assays for screening for protein kinase inhibitors applicable in cancer... 

Protein kinase inhibitors (PKIs) provide a promising therapeutic strategy for cancer chemotherapy. Phosphorylation of proteins is a universal mechanism for the control of many cellular processes. The phosphorylation of proteins occurs when the y-phosphate group of ATP is transferred to either tyrosine or serine/threonine within proteins. One family of enzymes catalyses tyrosine phosphorylation and another serine/threonine phosphorylation. Tyrosine phosphorylation is up-regulated in tumour cells and thus provides a selective target for therapy. Although there are numerous protein kinase stmctures, they have some features in common and the active site of the enzyme consists... 

Mikalsen T, Gerits N, Moens U (2006) Inhibitors of signal transduction protein kinases as targets for cancer therapy. Biotechnol Annu Rev 16 153-223... 

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