Design and Discovery of Small Molecules Targeting Raf-1 Kinase

Timothy   B.   Lowinger; Bernd      Riedl; Jacques      Dumas; Roger   A.   Smith

Abstract

Raf kinase, an enzyme which acts downstream in the Ras signaling pathway, is involved in cancerous cell proliferation. Thus, small molecule inhibitors of Raf kinase activity may be important agents for the treatment of cancer. A novel class of Raf-1 inhibitors was discovered, using a combination of medicinal and combinatorial chemistry approaches. This effort culminated in the identification of the clinical candidate BAY 43-9006, currently undergoing Phase I clinical trials. The present review summarizes the medicinal chemistry development of ureas as highly potent inhibitors of Raf-1 kinase.

Keywords: diphenyl ureas, bay 43-9006, raf-1 kinase, cancer, ras

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Current Pharmaceutical Design

Title: Design and Discovery of Small Molecules Targeting Raf-1 Kinase

Volume: 8 Issue: 25

Author(s): Timothy B. Lowinger, Bernd Riedl, Jacques Dumas and Roger A. Smith

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Keywords: diphenyl ureas, bay 43-9006, raf-1 kinase, cancer, ras

Abstract: Raf kinase, an enzyme which acts downstream in the Ras signaling pathway, is involved in cancerous cell proliferation. Thus, small molecule inhibitors of Raf kinase activity may be important agents for the treatment of cancer. A novel class of Raf-1 inhibitors was discovered, using a combination of medicinal and combinatorial chemistry approaches. This effort culminated in the identification of the clinical candidate BAY 43-9006, currently undergoing Phase I clinical trials. The present review summarizes the medicinal chemistry development of ureas as highly potent inhibitors of Raf-1 kinase.

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Cite this article as:

Lowinger B. Timothy, Riedl Bernd, Dumas Jacques and Smith A. Roger, Design and Discovery of Small Molecules Targeting Raf-1 Kinase, Current Pharmaceutical Design 2002; 8 (25) . https://dx.doi.org/10.2174/1381612023393125

DOI https://dx.doi.org/10.2174/1381612023393125	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286

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