Document Detail


Pharmacological targeting of CDK9 in cardiac hypertrophy.
MedLine Citation:
PMID:  19757441     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cardiac hypertrophy allows the heart to adapt to workload, but persistent or unphysiological stimulus can result in pump failure. Cardiac hypertrophy is characterized by an increase in the size of differentiated cardiac myocytes. At the molecular level, growth of cells is linked to intensive transcription and translation. Several cyclin-dependent kinases (CDKs) have been identified as principal regulators of transcription, and among these CDK9 is directly associated with cardiac hypertrophy. CDK9 phosphorylates the C-terminal domain of RNA polymerase II and thus stimulates the elongation phase of transcription. Chronic activation of CDK9 causes not only cardiac myocyte enlargement but also confers predisposition to heart failure. Due to the long interest of molecular oncologists and medicinal chemists in CDKs as potential targets of anticancer drugs, a portfolio of small-molecule inhibitors of CDK9 is available. Recent determination of CDK9's crystal structure now allows the development of selective inhibitors and their further optimization in terms of biochemical potency and selectivity. CDK9 may therefore constitute a novel target for drugs against cardiac hypertrophy.
Authors:
Vladimír Krystof; Ivo Chamrád; Radek Jorda; Jirí Kohoutek
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Medicinal research reviews     Volume:  30     ISSN:  1098-1128     ISO Abbreviation:  Med Res Rev     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-04-27     Completed Date:  2010-09-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8103150     Medline TA:  Med Res Rev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  646-66     Citation Subset:  IM    
Affiliation:
Faculty of Science, Laboratory of Growth Regulators, Palacký University & Institute of Experimental Botany AS CR, Slechtitelů 11, Olomouc 783 71, Czech Republic. vladimir.krystof@upol.cz
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Cardiomegaly / drug therapy*,  enzymology*
Cyclin T / chemistry
Cyclin-Dependent Kinase 9 / antagonists & inhibitors*,  chemistry,  metabolism
Drug Design
Humans
Molecular Sequence Data
Protein Kinase Inhibitors / chemistry,  metabolism,  pharmacology*,  therapeutic use*
Chemical
Reg. No./Substance:
0/Cyclin T; 0/Protein Kinase Inhibitors; EC 2.7.11.22/Cyclin-Dependent Kinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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