J 2010

PharmacologicalTargeting of CDK9 in CardiacHypertrophy

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

Základní údaje

Originální název

PharmacologicalTargeting of CDK9 in CardiacHypertrophy

Autoři

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

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 10.228

DOI

UT WoS

000278760700003

Klíčová slova anglicky

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

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 22. 7. 2012 08:18, Olga Křížová

Anotace

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.