Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014)
Veronika Malínková1, Jakub Vylíčil, Vladimír Kryštof
1a Palacký University and Institute of Experimental Botany AS CR, Centre of the Region Haná for Biotechnological and Agricultural Research, Laboratory of Growth Regulators , Šlechtitelů 11, CZ-78371 Olomouc, Czech Republic +420 585 634 854 ; +420 585 634 870 ; vladimir.krystof@upol.cz.
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 III 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.
Insights
Small molecule cyclin-dependent kinase (CDK) inhibitors are promising cancer therapeutics. Highly specific CDK4/CDK6 inhibitors show better clinical outcomes than pan-specific ones, driving research into new targeted drug candidates.
Area of Science:
- Oncology
- Medicinal Chemistry
- Drug Discovery
Background:
- Cell cycle deregulation is a hallmark of cancer.
- Cyclin-dependent kinases (CDKs) control cell cycle progression and are often dysregulated in cancer.
- Small molecule CDK inhibitors are emerging as targeted cancer therapeutics.
Purpose of the Study:
- To review patent applications for small molecule CDK inhibitors.
- To assess the landscape of CDK inhibitor development between 2009 and 2014.
- To identify trends in the pursuit of novel CDK-targeting drug candidates.
Main Methods:
- Systematic review of patent literature.
- Focus on small molecule inhibitors targeting CDKs.
- Analysis of patents published from 2009 to 2014.
Main Results:
- Significant patent activity in small molecule CDK inhibitor development.
- Emergence of highly specific CDK4/CDK6 inhibitors.
- Ongoing challenges in achieving selectivity due to conserved CDK active sites.
Conclusions:
- Highly specific CDK4/CDK6 inhibitors demonstrate superior clinical efficacy compared to pan-specific inhibitors.
- The development of selective mono-specific CDK inhibitors is a key area of research.
- Patient stratification for targeted therapy remains a critical challenge in CDK inhibitor development.
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