Clinical activity of tipifarnib in hematologic malignancies
Clinical activity of tipifarnib in hematologic malignancies
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DOI：
10.1517/13543784.16.3.381
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发表时间：
2007-02
影响因子：
6.1
通讯作者：
E. Jabbour;H. Kantarjian;J. Cortes
中科院分区：
文献类型：
--
作者：
E. Jabbour;H. Kantarjian;J. Cortes
法尼基转移酶抑制剂是一类竞争性抑制法尼基转移酶的新型抗癌药物。最初是为了抑制Ras激活所必需的法尼化而开发的，它们的作用机制似乎更复杂，涉及与Ras无关的其他蛋白质。在四类法尼基转移酶抑制剂中，至少有三种药物已被研究用于血液恶性肿瘤。Tipifarnib （R-115777）是一种口服非拟肽法尼基转移酶抑制剂，已显示出良好的临床活性。临床试验的初步结果显示酶靶抑制，可接受的毒性特征和有希望的临床活性证据。正在进行的研究将更好地确定蒂法尼的作用机制和与其他药物联合的作用，确定其在血液疾病治疗中的地位。
Farnesyltransferase inhibitors are a novel class of anticancer agents that competitively inhibit farnesyltransferase. Initially developed to inhibit the farnesylation that is necessary for Ras activation, their mechanism of action seems to be more complex, involving other proteins unrelated to Ras. Of the four classes of farnesyltransferase inhibitors, at least three agents have been investigated in hematologic malignancies. Tipifarnib (R-115777), an orally administered non-peptidomimetic farnesyltransferase inhibitor, has shown promising clinical activity. Preliminary results from clinical trials demonstrate enzyme target inhibition, an acceptable toxicity profile and promising evidence of clinical activity. Ongoing studies will better determine the mechanism of action of tipifarnib and the role of combination with other agents, defining its place in the therapeutic arsenal of hematologic disorders.