Recent advances in cyclin-dependent kinase inhibition. Purine-based derivatives as anti-cancer agents. Roles and perspectives for the future.
Recent advances in cyclin-dependent kinase inhibition. Purine-based derivatives as anti-cancer agents. Roles and perspectives for the future.
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DOI：
10.2174/1568026023393291
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发表时间：
2002-08
影响因子：
3.4
通讯作者：
J. Haesslein;N. Jullian
中科院分区：
文献类型：
--
作者：
J. Haesslein;N. Jullian
蛋白激酶（Ser/Thr和Tyr）在信号转导途径中起关键作用。已经表明，Cdk活性的失调与细胞增殖和癌症有关。抑制细胞周期蛋白依赖性激酶（Cdks）是潜在的新型抗癌药物的重要靶点。在发现Olomoucine之后，已经合成了广泛的三取代嘌呤衍生物，从而产生有效的Cdk抑制剂。这些嘌呤衍生的化合物与蛋白质的ATP口袋结合。感兴趣的结构为基础的药物设计，不同的晶体结构发表的日期显示的证据，嘌呤环的三种不同的结合模式，允许不同的探索ATP结合位点。一些合成和构效关系的例子进行了讨论的一组嘌呤衍生物，三取代的C-2，N-9和C-6。最后，在体内活动的审查，以及在其他治疗领域的应用。
Protein kinases (Ser/Thr and Tyr) play a key role in signal transduction pathways. It has been shown that deregulation of the Cdk activity is linked to cell proliferation and cancer. Inhibition of cyclin-dependent kinases (Cdks) is an important target for potential new anti-cancer drugs. Following the discovery of Olomoucine, a wide range of tri-substituted purine derivatives have been synthesized, leading to potent Cdk inhibitors. These purine-derived compounds bind to the ATP pocket of the protein. Of interest for structure-based drug design, the different crystal structures published to date show evidence for three different binding modes for the purine ring, allowing diverse exploration of the ATP binding site. Some examples of synthesis and structure activity relationships are discussed for a set of purine derivatives, tri-substituted on C-2, N-9 and C-6. Finally, in vivo activities are reviewed, as well as the applications in other therapeutic areas.