. "14"^^ . "14"^^ . . . "Projekt byl zam\u011B\u0159en na charakterizaci inhibitor\u016F cyklin-dependentn\u00EDch kinas (CDK), vyvinut\u00FDch na pracovi\u0161ti \u0159e\u0161itele d\u0159\u00EDve. Vyu\u017E\u00EDv\u00E1ny byly enzymologick\u00E9 a rentgenostrukturn\u00ED anal\u00FDzy inhibitor\u016F. D\u00E1le bylo studov\u00E1no antiproliferativn\u00ED a cytotoxick\u00E9 p\u016Fsoben\u00ED inhibitor\u016F CDK v\u00A0n\u00E1dorov\u00FDch bun\u011B\u010Dn\u00FDch lini\u00EDch se zam\u011B\u0159en\u00EDm na regulaci bun\u011B\u010Dn\u00E9ho cyklu, replikaci, opravy DNA homologn\u00ED rekombinac\u00ED, obecnou"@cs . . . "0"^^ . . "0"^^ . "1"^^ . . "During our previous projects we have developed several new inhibitors of cyclin-dependent kinases. Most of the described inhibitors showed a preference for CDK1 and CDK2, important regulators of the cell cycle. However, olomoucine II, which is a hydroxylderivative of well-known roscovitine, has much stronger antiproliferative activity than expected. Suprisingly, the compound showed interesting preference to CDK9, important regulator of elongation phase of transcription. Simultaneously, we have identified CAN508, novel highly selective CDK9 inhibitor. The project is therefore aimed at detailed biochemical characterization of selectivity of these inhibitors by means of enzymological studies and molecular modeling. The effect of the inhibitors oncancer cell lines will be analyzed as well, with a specific focus on general transcription, activation of tumour suppressor p53 and interactions with modern anticancer drugs. Such selective pharmacological inhibitors of CDK9 are still not available and"@en . . . . "Biologick\u00E1 aktivita syntetick\u00FDch inhibitor\u016F cyklin-dependentn\u00EDch kinas" . . . "inhibitor; olomoucine II; roscovitine; cyclin-dependent kinase"@en . "GA204/08/0511" . "2010-12-31+01:00"^^ . "2008-01-01+01:00"^^ . . . . "B\u011Bhem \u0159e\u0161en\u00ED p\u0159edchoz\u00EDch projekt\u016F jsme p\u0159ipravili \u0159adu nov\u00FDch inhibitor\u016F cyklin-dependentn\u00EDch kinas (CDK). V\u011Bt\u0161ina inhibitor\u016F vykazovala preferenci k CDK1 a CDK2, co\u017E jsou d\u016Fle\u017Eit\u00E9 regul\u00E1tory bun\u011B\u010Dn\u00E9ho cyklu. Olomoucin II, deriv\u00E1t zn\u00E1m\u00E9ho roskovitinu, v\u0161ak m\u00E1 oproti o\u010Dek\u00E1v\u00E1n\u00ED v\u00FDrazn\u011B siln\u011Bj\u0161\u00ED antiprolifera\u010Dn\u00ED \u00FA\u010Dinky. Tyto p\u0159ipisujeme siln\u00E9 inhibici CDK9, v\u00FDznamn\u00E9mu regul\u00E1toru elonga\u010Dn\u00ED f\u00E1ze transkripce. Z\u00E1rove\u0148 jsme identifikovali CAN508 jako vysoce selektivn\u00ED inhibitor CDK9. Tento projekt je proto zam\u011B\u0159en na detailn\u00ED charakterizaci a selektivitu t\u011Bchto inhibitor\u016F, a to jak klasick\u00FDmi enzymologick\u00FDmi studiemi, tak i molekul\u00E1rn\u00EDm modelov\u00E1n\u00EDm. Z\u00E1rove\u0148 budeme sledovat vliv inhibitor\u016F na n\u00E1dorov\u00E9 bun\u011B\u010Dn\u00E9 linie se zvl\u00E1\u0161tn\u00EDm z\u0159etelem na obecnou transkripci, aktivaci n\u00E1dorov\u00E9ho supresoru p53 a interakci s vybran\u00FDmi modern\u00EDmi cytostatiky. Vysoce selektivn\u00ED inhibitory CDK9 s mo\u017En\u00FDm farmakologick\u00FDm uplatn\u011Bn\u00EDm doposud nejsou zn\u00E1my, proto se tyto l\u00E1tky mohou st\u00E1t v\u00FDznam\u00FDmi n\u00E1stroji pro studium funkc\u00ED" . " olomoucine II" . "Biological activity of synthetic inhibitors of cyclin-dependent kinases"@en . . " roscovitine" . "http://www.isvav.cz/projectDetail.do?rowId=GA204/08/0511"^^ . . "2010-04-16+02:00"^^ . . "inhibitor" . "The project was dedicated to characterizaton of cyclin-dependent kinase (CDK) inhibitors, that had been developed in the laboratory during past projects, by means of enzymological assays and X-ray crystallography. Emphasis was laid also on antiproliferative and cytotoxic effect of studied CDK inhibitors in human cancer cell lines, with a focus on cell cycle regulation, DNA replication, homologous"@en . "2015-02-09+01:00"^^ . .