Protein tyrosine kinase inhibitors as anticancer agents

There are > 700 protein kinases and 100 protein phosphatases encoded within the human genome. By catalysing protein phosphorylation and dephosphorylation, they play a pivotal role in intracellular signalling and in the regulation of signal transduction pathways. Activation of oncogenes coding for such proteins can lead to the production of kinases that are continually active in the absence of a normal stimulus, leading to increased cell proliferation and/or decreased apoptosis. Receptor and non-receptor protein tyrosine kinases (PTKs) are essential enzymes in cellular signalling processes that regulate cell growth, differentiation, migration and metabolism. Their inhibition by specific inhibitors was recently shown to constitute a new modality for cancer treatment. A patent literature review comprising the years 2000-2003 is presented here, as the major drug houses are currently involved in the design and development of novel types of such compounds with applications as antitumour agents.