Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009-2014)

被引:32
|
作者
Malinkova, Veronika
Vylicil, Jakub
Krystof, Vladimir [1 ]
机构
[1] Palacky Univ, CZ-78371 Olomouc, Czech Republic
关键词
cancer; CDK; cyclin; inhibitor; kinase; TROPOMYOSIN RECEPTOR KINASE; CELL-CYCLE; HEPATOCELLULAR-CARCINOMA; SYNTHETIC LETHALITY; PHASE-I; TRANSCRIPTION; CDK1; PHARMACOKINETICS; TOLERABILITY; SENSITIVITY;
D O I
10.1517/13543776.2015.1045414
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Introduction: Cell cycle deregulation is a common characteristic of cancer cells. Progression through the cell cycle is controlled by enzymes known as cyclin-dependent kinases (CDKs), whose activity can be upregulated by a wide range of molecular mechanisms. Based on these observations, small molecule CDK inhibitors are being developed as potential cancer therapeutics. Some of these compounds have entered Phase Ill clinical trials and one of them, palbociclib, recently received accelerated approval from the FDA. However, the complexity of CDK biology and the undesired side effects of the existing inhibitors mean that the hunt for new CDK-targeting drug candidates continues. Areas covered: This article reviews patent applications related to small molecule CDK inhibitors published between 2009 and 2014. Expert opinion: Clinical trials with pan-specific inhibitors have generally yielded unambiguously positive outcomes. However, better results have been achieved with highly specific inhibitors of CDK4/CDK6. This may be due to several factors and has generated considerable interest in the discovery of new mono-specific CDK inhibitors. The development of such compounds is challenging because all CDKs have very similar active sites. Aside from this issue of selectivity, another key challenge is the identification of patients who will benefit from specific therapies.
引用
收藏
页码:953 / 970
页数:18
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