Ruthenium-based chemotherapeutics: are they ready for prime time?
Ruthenium-based chemotherapeutics: are they ready for prime time?
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DOI：
10.1007/s00280-010-1293-1
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发表时间：
2010-05
影响因子：
3
通讯作者：
Emadi, Ashkan
中科院分区：
文献类型：
--
作者：
Antonarakis, Emmanuel S.;Emadi, Ashkan
自发现顺铂以来，许多过渡金属配合物被合成并测定其抗肿瘤活性。近年来，钌基分子已成为有前途的抗肿瘤和抗转移药物，在铂耐药肿瘤或铂的替代品中具有潜在的用途。理论上，钌化合物具有独特的生化特性，使其优先在肿瘤组织中积累，只有在进入肿瘤细胞后才能转化为活性状态。有趣的是，一些钌制剂显示出对癌症转移的显著活性，但对原发肿瘤的影响很小。两种钌基药物NAMI-A和KP1019已进入人体临床试验阶段。本文将重点介绍这两种铅钌化合物的化学性质、作用机制、临床前数据和早期临床结果。其他有前途的钌药物也将进行回顾，重点是新型钌化合物ONCO4417和DW1/2，它们在临床前系统中显示出Pim-1激酶抑制作用。这些和其他钌制剂的进一步发展可能依赖于新的方法，包括合理的联合策略，以及识别药物活性的潜在药效学生物标志物，以帮助早期临床研究。
Since the discovery of cis-platinum, many transition metal complexes have been synthesized and assayed for antineoplastic activity. In recent years, ruthenium-based molecules have emerged as promising antitumor and anti-metastatic agents with potential uses in platinum-resistant tumors or as alternatives to platinum. Ruthenium compounds theoretically possess unique biochemical features allowing them to accumulate preferentially in neoplastic tissues and to convert to their active state only after entering tumor cells. Intriguingly, some ruthenium agents show significant activity against cancer metastases but have minimal effects on primary tumors. Two ruthenium-based drugs, NAMI-A and KP1019, have reached human clinical testing. This review will highlight the chemical properties, mechanism of action, preclinical data, and early phase clinical results of these two lead ruthenium compounds. Other promising ruthenium agents will also be reviewed with emphasis on the novel ruthenium compound ONCO4417, and DW1/2 that has demonstrated Pim-1 kinase inhibition in preclinical systems. Further development of these and other ruthenium agents may rely on novel approaches including rational combination strategies as well as identification of potential pharmacodynamic biomarkers of drug activity aiding early phase clinical studies.
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DOI：
10.1124/jpet.104.073395
发表时间：
2005-01-01
影响因子：
3.5
作者：
Heffeter, P;Pongratz, M;Berger, W
通讯作者：
Berger, W
影响因子：
16.6
作者：
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影响因子：
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作者：
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通讯作者：
Jodrell, D I
影响因子：
9.7
作者：
Kapitza, S;Jakupec, MA;Marian, B
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影响因子：
2.6
作者：
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