title: Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).
abstract: BACKGROUND
  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.
  
  
  METHODS
  This article reviews patent applications related to small molecule CDK inhibitors published between 2009 and 2014.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a 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.
authors.forename: Veronika
authors.initials: V
authors.lastname: Malínková
authors.forename: Jakub
authors.initials: J
authors.lastname: Vylíčil
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kryštof
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D017277:Drug Approval; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases
keywords: CDK; cancer; cyclin; inhibitor; kinase