细胞周期蛋白依赖激酶
激酶
CDK抑制剂
细胞周期蛋白依赖激酶1
小分子
细胞周期
生物
细胞周期蛋白依赖激酶7
细胞生物学
细胞周期蛋白依赖激酶2
癌症研究
生物化学
蛋白激酶A
细胞
作者
Hiroshi Hirai,Nobuhiko Kawanishi,Yoshikazu Iwasawa
标识
DOI:10.2174/1568026053507688
摘要
Loss of normal cell cycle regulation is the hallmark of human cancers, and alteration of the components involved in cell cycle regulation occurs in most human tumors. This suggests that Cyclin dependent kinases (CDKs) are an attractive target for the development of pharmacological agents for the treatment of cancer. Recently, CDK family members that are not directly involved in cell cycle regulation have been identified. This includes CDK7, CDK8, and CDK9, which participate in transcription regulation, and CDK5, which plays a role in neuronal and secretory functions. Given the involvement of CDKs in multiple cellular processes, development of selective small molecule inhibitors for specific CDKs is expected to help clarify whether improved specificity of cell cycle CDK inhibitors will enhance their therapeutic potential in cancer treatment. Selective inhibitors are also needed as tools to explore the biology of diseases in which CDKs may participate and to help develop therapeutics to treat them. Intensive screening and drug design based on CDK/inhibitor co-crystal structure and SAR studies have led to the identification of a large variety of chemical inhibitors of CDKs. Although they are competitive with ATP at the catalytic site, their kinase selectivity varies greatly, and inhibitors selective for certain CDKs have begun to be identified. There are currently two categories of selective CDK inhibitors: those that are selective for CDK2 and CDK1 and those that are selective for CDK4/6. These two types of inhibitors have different effects on tumor cells and are expected to be useful in the treatment of cancer. Keywords: cyclin-dependent kinase, cdk4, cdk6, cdk2, cdk inhibitor
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