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Arylazopyrazole AAP1742 Inhibits CDKs and Induces Apoptosis in Multiple Myeloma Cells via Mcl-1 Downregulation
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SYSNO ASEP 0433741 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Arylazopyrazole AAP1742 Inhibits CDKs and Induces Apoptosis in Multiple Myeloma Cells via Mcl-1 Downregulation Author(s) Jorda, Radek (UEB-Q) ORCID, RID
Navrátilová, Jana (UEB-Q)
Hušková, Zlata (UEB-Q)
Schütznerová, E. (CZ)
Cankař, P. (CZ)
Strnad, Miroslav (UEB-Q) RID, ORCID
Kryštof, Vladimír (UEB-Q) RID, ORCIDSource Title Chemical Biology & Drug Design. - : Wiley - ISSN 1747-0277
Roč. 84, č. 4 (2014), s. 402-408Number of pages 7 s. Language eng - English Country GB - United Kingdom Keywords CAN508 ; cyclin-dependent kinase ; inhibitor Subject RIV EB - Genetics ; Molecular Biology R&D Projects GAP305/12/0783 GA ČR - Czech Science Foundation (CSF) GA14-19590S GA ČR - Czech Science Foundation (CSF) LO1204 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UEB-Q - RVO:61389030 UT WOS 000342978400003 DOI 10.1111/cbdd.12330 Annotation Inhibitors of cyclin-dependent kinases 9 have been developed as potential anticancer drugs for the treatment of multiple myeloma. We have previously prepared a library of arylazo-3,5-diaminopyrazole inhibitors of CDKs. Here, we describe a novel member, AAP1742 (CDK9 inhibition with IC50 =0.28mum), that reduces the viability of multiple myeloma cell lines in low micromolar concentrations. Consistent with inhibition of CDK9, AAP1742 decreases the phosphorylation of RNA polymerase II and inhibits mRNA synthesis of anti-apoptotic proteins Mcl-1, Bcl-2, and XIAP, followed by apoptosis in the RPMI-8226 cell line in a dose- and a time-dependent manner. These results are consistent with the biochemical profile of AAP1742 and further suggest cellular inhibition of CDK9 as a possible target for anticancer drugs. Workplace Institute of Experimental Botany Contact David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Year of Publishing 2015 Electronic address http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=MEDLINE&DestLinkType=FullRecord&UT=24803299
Number of the records: 1