title: Overview of CDK9 as a target in cancer research.
abstract: CDK9 is a protein in constant development in cancer therapy. Herein we present an overview of the enzyme as a target for cancer therapy. We provide data on its characteristics and mechanism of action. In recent years, CDK9 inhibitors that have been designed with molecular modeling have demonstrated good antitumoral activity in vitro. Clinical studies of the drugs flavopiridol, dinaciclib, seliciclib, SNS-032 and RGB-286638 used as CDK9 inhibitors are also reviewed, with their additional targets and their relative IC50 values. Unfortunately, treatment with these drugs remains unsuccessful and involves many adverse effects. We could conclude that there are many small molecules that bind to CDK9, but their lack of selectivity against other CDKs do not allow them to get to the clinical use. However, drug designers currently have the tools needed to improve the selectivity of CDK9 inhibitors and to make successful treatment available to patients.
authors.affiliation: a Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University , Philadelphia , PA , USA.
authors.forename: Fatima
authors.initials: F
authors.lastname: Morales
authors.affiliation: a Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University , Philadelphia , PA , USA.|b Department of Medicine , Surgery and Neuroscience, University of Siena , Siena , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D003497:Cyclic N-Oxides; D042863:Cyclin-Dependent Kinase 9 / Q000037:antagonists & inhibitors / Q000235:genetics*; D005419:Flavonoids / Q000627:therapeutic use; D006801:Humans; D007212:Indolizines; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010080:Oxazoles / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000627:therapeutic use; D000077546:Roscovitine; D013844:Thiazoles / Q000627:therapeutic use; D014508:Urea / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D003497:Cyclic N-Oxides; D005419:Flavonoids; D007212:Indolizines; C484864:N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide; D010080:Oxazoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011687:Purines; D011720:Pyrazoles; D011726:Pyridinium Compounds; C546217:RGB 286638; D013844:Thiazoles; D000077546:Roscovitine; C077990:alvocidib; C553669:dinaciclib; D014508:Urea; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9
keywords: CDK9; anticancer; antitumor; cyclin; drug development; kinase; molecular modeling