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Development of Small-Molecule Inhibitors of Raf

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Abstract:

Raf proteins are key components in the signal transduction of the Ras/Raf/MEK/ERK pathway, which is pivotal in oncogenesis, tumor cell malignancy, viral infection, neuronal degeneration, and lymphocyte activation. A number of gain-of-function mutations of Raf genes have been detected in various cancer cells. Consequently, Raf as an anticancer target has been intensively investigated. Numerous small-molecule Raf-inhibiting compounds have been reported in the literature and in patent applications. One of such compounds, the urea derivative Bay 43-9006, has been subjected to the most extensive clinical trials on cancer, including phase III trials, and results to date indicate that this agent can provide clinical benefit without obvious toxicity. Small-molecule Raf inhibitors have also been evaluated preclinically for treatment of viral infection, neuronal degeneration, and inflammatory disease. Thus, small molecule inhibitors of Raf may have broad applications in addition to cancer therapy.





Keywords: A-Raf; B-Raf; MAP kinases; Raf-1; Ras; anticancer agents; small molecule; virus infection

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/157489106777452665

Affiliations: Department of Thoracic and Cardiovascular Surgery, Unit 445, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4009, USA.

Publication date: June 1, 2006

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  • Recent Patents on Anti-Infective Drug Discovery publishes review articles on recent patents in the field of anti-infective drug discovery e.g. on novel bioactive compounds, analogs & targets. A selection of important and recent patents on anti-infective drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-infective drug design and discovery.
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