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Review

Nature Reviews Drug Discovery 5, 835–844 (1 October 2006) | doi:10.1038/nrd2130

Discovery and development of sorafenib: a multikinase inhibitor for treating cancer

Scott Wilhelm , Christopher Carter , Mark Lynch , Timothy Lowinger , Jacques Dumas , Roger A. Smith , Brian Schwartz , Ronit Simantov & Susan Kelley

Since the molecular revolution of the 1980s, knowledge of the aetiology of cancer has increased considerably, which has led to the discovery and development of targeted therapies tailored to inhibit cancer-specific pathways. The introduction and refinement of rapid, high-throughput screening technologies over the past decade has greatly facilitated this targeted discovery and development process. Here, we describe the discovery and continuing development of sorafenib (previously known as BAY 43-9006), the first oral multikinase inhibitor that targets Raf and affects tumour signalling and the tumour vasculature. The discovery cycle of sorafenib (Nexavar; Bayer Pharmaceuticals) — from initial screening for a lead compound to FDA approval for the treatment of advanced renal cell carcinoma in December 2005 — was completed in just 11 years, with approval being received |[sim]|5 years after the initiation of the first Phase I trial.