Metabolism considerations for kinase inhibitors in cancer treatment.
Metabolism considerations for kinase inhibitors in cancer treatment.
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DOI：
10.1517/17425255.2010.506873
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发表时间：
2010-10
影响因子：
4.3
通讯作者：
Cameron MD
中科院分区：
文献类型：
--
作者：
Duckett DR;Cameron MD
在过去的十年里，制药业的共同努力导致了蛋白激酶抑制剂作为某些癌症的有效靶向治疗的临床开发的成功。这篇综述详细介绍了截至2010年3月在美国或欧洲被批准用于癌症治疗的八种小分子激酶抑制剂：伊马替尼、索拉非尼、吉非替尼、厄洛替尼、达沙替尼、拉帕替尼、舒尼替尼和尼洛替尼。这八种化合物从相对特定的抑制剂拉帕替尼，到更混杂的激酶抑制剂达沙替尼和苏尼替尼，都不同。简要讨论了每种抑制剂的生物学特性、对其他酶的选择性和毒性。对每种化合物的代谢、药物转运体、药物-药物相互作用以及代谢在化合物毒性中的可能作用提供了更详细的讨论。目前批准的大多数激酶抑制剂受药物转运体的影响很大，并且受CYP3A4抑制剂/诱导剂的影响很大。至少三种药物，吉非替尼、厄洛替尼和达沙替尼被代谢成能够与生物分子共价结合的反应性代谢物。
A concerted effort by the pharmaceutical industry over the last decade has led to the successful clinical development of protein kinase inhibitors as effective targeted therapies for certain cancers. This review details the eight small molecule kinase inhibitors that have been approved for the treatment of cancer in either the United States or Europe as of March 2010: imatinib, sorafenib, gefitinib, erlotinib, dasatinib, lapatinib, sunitinib and nilotinib. These eight compounds vary from the relatively specific inhibitor lapatinib, to the more promiscuous kinase inhibitors dasatinib and sunitinib. A brief discussion on the biology of each inhibitor, selectivity over other kinases, and toxicity are provided. More detailed discussion on metabolism, drug transporters, drug-drug interactions, and the possible roles of metabolism in compound toxicity is provided for each compound. The majority of the currently approved kinase inhibitors are heavily influenced by drug transporters and significantly affected by CYP3A4 inhibitors/inducers. At least three, gefitinib, erlotinib, and dasatinib, are metabolized to form reactive metabolites capable of covalently binding biomolecules.
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影响因子：
11.2
作者：
Dai CL;Tiwari AK;Wu CP;Su XD;Wang SR;Liu DG;Ashby CR Jr;Huang Y;Robey RW;Liang YJ;Chen LM;Shi CJ;Ambudkar SV;Chen ZS;Fu LW
通讯作者：
Fu LW
影响因子：
158.5
作者：
Druker, Brian J.;Guilhot, Francois;Larson, Richard A.
通讯作者：
Larson, Richard A.
影响因子：
45.3
作者：
Baselga, J;Rischin, D;Albanell, J
通讯作者：
Albanell, J
影响因子：
5.8
作者：
Bergman, Ebba;Forsell, Patrik;Lennernaes, Hans
通讯作者：
Lennernaes, Hans
影响因子：
3
作者：
Britten, Carolyn D.;Kabbinavar, Fairooz;Slamon, Dennis
通讯作者：
Slamon, Dennis