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B-Raf激酶的第600号氨基酸残基缬氨酸(V)突变成谷氨酸(E),成为与癌症相关的激酶,高表达的B-Raf V600E可引发黑色素瘤。维罗非尼是B-Raf V600E特异性抑制剂,临床治疗晚期黑色素瘤,故得名vemurafenib。维罗非尼的研制也是自1996年Shuker等开创了基于片段的药物发现(FBDD)的方法以来(Shuker SB,et al.Science,1996,274:1531),用FBDD方法创制成功的第一个药物。1治疗黑色素瘤的靶标BRAF是人类最重要的原癌基因之一,大约8%的肿瘤发生BRAF突变,多为V600E突变体,突变产
B-Raf kinase, the 600th amino acid residue valine (V), is mutated to glutamate (E), a cancer-associated kinase, and B-Raf V600E, a highly expressed protein, can trigger melanoma. Vemurafenib is a specific inhibitor of B-Raf V600E, clinical treatment of advanced melanoma, hence the name vemurafenib. The development of vemurafenib has also been the first successful FBDD method since Shuker et al. Initiated the method of fragment-based drug discovery (FBDD) in 1996 (Shuker SB, et al. Science, 1996, 274: 1531) drug. 1 target of treatment of melanoma BRAF is one of the most important human oncogene, about 8% of tumors BRAF mutations occur, mostly V600E mutant, mutant