Highlights of the Latest Advances in Research on CDK Inhibitors.

Highlights of the Latest Advances in Research on CDK Inhibitors.
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DOI:
10.3390/cancers6042224
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发表时间:
2014-10-27
期刊:
影响因子:
5.2
通讯作者:
Valius M
Valius M
中科院分区:
医学2区
文献类型:
--
作者:
Cicenas J;Kalyan K;Sorokinas A;Jatulyte A;Valiunas D;Kaupinis A;Valius M

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不受控制的增殖是癌症和其他增殖性疾病的标志,因此,异常的细胞周期调节在这些疾病中很常见。细胞周期蛋白依赖性激酶(CDKs)在控制细胞周期和增殖中起着至关重要的作用。这些激酶在各种癌症、病毒感染、神经退行性疾病、缺血和一些增殖性疾病中经常失调。这导致了对用于治疗用途的小分子CDK抑制剂的严格追求。早期用非选择性CDK抑制剂阻断CDK的努力缺乏特异性和有效性,但有明显的毒性,但最近选择性CDK抑制剂的进展使得首次成功地将这些激酶靶向治疗几种疾病。目前正在进行的主要工作是开发CDK抑制剂作为单一疗法和与化疗和其他靶向药物的合理组合。
Uncontrolled proliferation is the hallmark of cancer and other proliferative disorders and abnormal cell cycle regulation is, therefore, common in these diseases. Cyclin-dependent kinases (CDKs) play a crucial role in the control of the cell cycle and proliferation. These kinases are frequently deregulated in various cancers, viral infections, neurodegenerative diseases, ischemia and some proliferative disorders. This led to a rigorous pursuit for small-molecule CDK inhibitors for therapeutic uses. Early efforts to block CDKs with nonselective CDK inhibitors led to little specificity and efficacy but apparent toxicity, but the recent advance of selective CDK inhibitors allowed the first successful efforts to target these kinases for the therapies of several diseases. Major ongoing efforts are to develop CDK inhibitors as monotherapies and rational combinations with chemotherapy and other targeted drugs.
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