A Novel Roscovitine Derivative Potently Induces G(1)-Phase Arrest in Platelet-Derived Growth Factor-BB-Activated Vascular Smooth Muscle Cells

0344007 - ÚEB 2011 RIV US eng J - Journal Article
Sroka, I. M. - Heiss, E.H. - Havlíček, Libor - Totzke, F. - Aristei, Y. - Pechan, P. - Kubbutat, M.H.G. - Strnad, Miroslav - Dirsch, V.M.
A Novel Roscovitine Derivative Potently Induces G(1)-Phase Arrest in Platelet-Derived Growth Factor-BB-Activated Vascular Smooth Muscle Cells.
Molecular Pharmacology. Roč. 77, č. 2 (2010), s. 255-261. ISSN 0026-895X. E-ISSN 1521-0111
R&D Projects: GA ČR GA301/08/1649
Grant - others:_(XE) LSHB-CT-2004-503467
Institutional research plan: CEZ:AV0Z50380511
Keywords : CYCLIN-DEPENDENT KINASES * DRUG-ELUTING STENTS * CYC202 R-ROSCOVITINE
Subject RIV: FD - Oncology ; Hematology
Impact factor: 4.725, year: 2010

Abnormal vascular smooth muscle cell (VSMC) proliferation contributes to the pathogenesis of restenosis. Thus, drugs interfering with cell cycle progression in VSMC are promising candidates for an antirestenotic therapy. In this study, we pharmacologically characterize N-5-(2-aminocyclohexyl)-N-7-benzyl-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyrimidine-5,7-di-amine (LGR1406), a novel derivative of the cyclin-dependent kinase (CDK) inhibitor roscovitine (ROSC), in PDGF-BB-activated VSMC. Cell proliferation was quantified measuring DNA synthesis via 5-bromo-2'-deoxyuridine incorporation. Analysis of cell cycle distribution was done by flow cytometry using propidium iodide-stained nuclei. Key regulators of the cell cycle and relevant signaling pathways were dissected by Western blot analyses. In addition, in vitro kinase assays and in silico studies regarding the pharmacokinetic profile of both compounds were performed.
Permanent Link: http://hdl.handle.net/11104/0186345