Discovery and development of sorafenib: a multikinase inhibitor for treating cancer
Discovery and development of sorafenib: a multikinase inhibitor for treating cancer
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DOI：
10.1038/nrd2262
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发表时间：
2007
影响因子：
120.1
通讯作者：
S. Wilhelm;Christopher A. Carter;M. Lynch;T. Lowinger;J. Dumas;Roger A. Smith;B. Schwartz;R. Siman
中科院分区：
文献类型：
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作者：
S. Wilhelm;Christopher A. Carter;M. Lynch;T. Lowinger;J. Dumas;Roger A. Smith;B. Schwartz;R. Siman
自 20 世纪 80 年代的分子革命以来，对癌症病因学的了解显着增加，这导致了针对抑制癌症特异性途径的靶向疗法的发现和开发。过去十年中快速、高通量筛选技术的引入和完善极大地促进了这一有针对性的发现和开发过程。在这里，我们描述了索拉非尼（以前称为 BAY 43-9006）的发现和持续开发，索拉非尼是第一个靶向 Raf 并影响肿瘤信号传导和肿瘤脉管系统的口服多激酶抑制剂。索拉非尼（Nexavar；拜耳制药）的发现周期——从先导化合物的初步筛选到 FDA 于 2005 年 12 月批准用于治疗晚期肾细胞癌——仅用了 11 年时间就完成了，并在第一个 I 期试验开始约 5 年后获得批准。
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 ∼5 years after the initiation of the first Phase I trial.