PharmacologicalTargeting of CDK9 in CardiacHypertrophy

J 2010

PharmacologicalTargeting of CDK9 in CardiacHypertrophy

KRYŠTOF, Vladimír, Ivo CHAMRÁD, Radek JORDA and Jiří KOHOUTEK

Basic information

Original name

PharmacologicalTargeting of CDK9 in CardiacHypertrophy

Authors

KRYŠTOF, Vladimír, Ivo CHAMRÁD, Radek JORDA and Jiří KOHOUTEK

Edition

Medicinal Research Reviews, WILEY-BLACKWELL, 2010, 0198-6325

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 10.228

DOI

http://dx.doi.org/10.1002/med.20172

UT WoS

000278760700003

Keywords in English

P-TEFb; cardiac myocyte; cardiac hypertrophy; protein kinase; inhibitor

Abstract

V originále

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.

Citovat

KRYŠTOF, Vladimír, Ivo CHAMRÁD, Radek JORDA and Jiří KOHOUTEK. PharmacologicalTargeting of CDK9 in CardiacHypertrophy. Medicinal Research Reviews. WILEY-BLACKWELL, 2010, vol. 30, No 4, p. 646-666, 20 pp. ISSN 0198-6325. Available from: https://dx.doi.org/10.1002/med.20172.

@article{987489,
   author = {Kryštof, Vladimír and Chamrád, Ivo and Jorda, Radek and Kohoutek, Jiří},
   article_number = {4},
   doi = {http://dx.doi.org/10.1002/med.20172},
   keywords = {P-TEFb; cardiac myocyte; cardiac hypertrophy; protein kinase; inhibitor},
   language = {eng},
   issn = {0198-6325},
   journal = {Medicinal Research Reviews},
   title = {PharmacologicalTargeting of CDK9 in CardiacHypertrophy},
   url = {http://onlinelibrary.wiley.com/doi/10.1002/med.20172/abstract},
   volume = {30},
   year = {2010}
}

TY  - JOUR
ID  - 987489
AU  - Kryštof, Vladimír - Chamrád, Ivo - Jorda, Radek - Kohoutek, Jiří
PY  - 2010
TI  - PharmacologicalTargeting of CDK9 in CardiacHypertrophy
JF  - Medicinal Research Reviews
VL  - 30
IS  - 4
SP  - 646-666
EP  - 646-666
PB  - WILEY-BLACKWELL
SN  - 01986325
KW  - P-TEFb
KW  - cardiac myocyte
KW  - cardiac hypertrophy
KW  - protein kinase
KW  - inhibitor
UR  - http://onlinelibrary.wiley.com/doi/10.1002/med.20172/abstract
N2  - 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.
ER  -

KRYŠTOF, Vladimír, Ivo CHAMRÁD, Radek JORDA and Jiří KOHOUTEK. PharmacologicalTargeting of CDK9 in CardiacHypertrophy. \textit{Medicinal Research Reviews}. WILEY-BLACKWELL, 2010, vol.~30, No~4, p.~646-666, 20 pp. ISSN~0198-6325. Available from: https://dx.doi.org/10.1002/med.20172.

Detailed Information on Publication Record