"Neuvedeno."@en . "1"^^ . "V\u00FDvoj nov\u00E9 generace inhibitor\u016F cyklin-dependentn\u00EDch kinas:vztahy mezi strukturou a aktivitou, molekul\u00E1rn\u00ED a in vitro mechanismy \u00FA\u010Dinku" . . . . . . "0"^^ . . "GA303/02/0875" . . . . . . . "http://www.isvav.cz/projectDetail.do?rowId=GA303/02/0875"^^ . "We have discovered unusual specificity of purine derivative olomoucine (OC; 2-(2-hydroxyethylamino)- 6-benzylamino-9-methylpurine) toward cell cycle kinases (CDK1, CDK2, CDK5, ERK1). The design and inhibitory activity of OC was further improved by modifications at positions 2,6 and 9. This has recently led to discovery of roscovitine, olomoucine II, and purvalanol, which displays an enhanced inhibitory activity toward CDK1, an increased antimitotic activity at the G1/S and G2/M points of the cell cycle, and stronger and more selective antitumour effects. In this grant we would like: (1)to prepare new generation of triazole CDK inhibitors, (2)to study their structure-activity relationship in different kinase assays, (5)to test the cytotoxic, apoptotic and cell cycle effects of novel derivatives, (6) to study pharmacokinetics and metabolism in vitro and in vivo, (7) to study molecular mechanims of action in cell division cycle, and (8)to co-crystalise the most effective inhibitor with CDK2"@en . . . "Objev olomoucinu jako prv\u00E9ho selektivn\u00EDho inhibitoru CDK (CDKI) p\u0159inesl v\u00FDvoj \u00FA\u010Dinn\u011Bj\u0161\u00EDch CDKI, nap\u0159. roskovitinu, purvalanolu a olomoucinu II. Na\u0161\u00EDm z\u00E1m\u011Brem bylo pokra\u010Dovat ve v\u00FDvoji CDKI s\u00A0c\u00EDlem nalezen\u00ED slou\u010Denin \u00FA\u010Dinn\u011Bj\u0161\u00EDch, slou\u010Denin s\u00A0modifikovanou"@cs . "8"^^ . . "2008-06-02+02:00"^^ . "8"^^ . "Development of new generation of cyclin-dependent kinase inhibitors: structure-activity relationships, molecular and in vitro mechanisms of action"@en . "Objev olomoucinu jako prvn\u00EDho \u00FA\u010Dinn\u00E9ho inhibitoru CDK p\u0159inesl v\u00FDvoj nov\u00E9 generace purinov\u00FDch l\u00E1tek, nap\u0159. roskovitinu, purvalanolu a olomoucinu II. Na\u0161\u00EDm c\u00EDlem je nejen pokra\u010Dovat ve v\u00FDvoji dal\u0161\u00EDch, je\u0161t\u011B \u00FA\u010Dinn\u011Bj\u0161\u00EDch inhibitor\u016F CDK, ale zejm\u00E9na vyvinout nov\u00E9 generace nepurinov\u00FDch inhibitor\u016F. C\u00EDlem tohoto projektu je p\u0159\u00EDprava nov\u00FDch inhibitor\u016F CDK na b\u00E1zi triazol\u016F, kter\u00E1 bude zahrnovat: (1) p\u0159ipravit nov\u00E9 typy inhibitor\u016F CDK odvozen\u00FDch od triazol\u016F, (2) studovat vztahy mezi strukturou a aktivitou v r\u016Fzn\u00FDch kinasov\u00FDch testech, (5) testovat \u00FA\u010Dinky cytotoxick\u00E9, apoptoick\u00E9 a na bun\u011B\u010Dn\u00FD cyklus u \u017Eivo\u010Di\u0161n\u00FDch i rostlinn\u00FDch bun\u011Bk, (6) studovat farmakokinetiku a metabolismus in vitro a in vivo, (7) studovat protin\u00E1dorovou \u00FA\u010Dinnost nov\u00FDch deriv\u00E1t\u016F in vivo, a(8) a pokusit se o p\u0159\u00EDpravu co-krystal\u016F nej\u00FA\u010Dinn\u011Bj\u0161\u00EDho deriv\u00E1tu s\u00A0CDK2 a jejich anal\u00FDzu pomoc\u00ED X-ray krystalografie. P\u0159edpokl\u00E1d\u00E1me, \u017Ee v\u00FDstupem z tohoto projektu budou p\u0159edev\u0161\u00EDm publikace v presti\u017En\u00EDch zahrani\u010Dn\u00EDch \u010Dasopisech a rovn\u011B\u017E mezin\u00E1rodn\u011B" . "The discovery of olomoucine, the first selective inhibitor of CDK (CDKI) triggered the development of more efficient CDKI, e.g. roscovitine, purvalanol and olomoucine II. We further explored CDKI in order to find more effective compounds, derivatives wit"@en . . . . . "1"^^ . . .