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A Novel Series of Highly Potent 2,6,9-Trisubstituted Purine Cyclin-Dependent Kinase Inhibitors

SYSNO ASEP	0399222
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	A Novel Series of Highly Potent 2,6,9-Trisubstituted Purine Cyclin-Dependent Kinase Inhibitors
Author(s)	Gucký, T. (CZ) Jorda, Radek (UEB-Q)_{ORCID, RID} Zatloukal, M. (CZ) Bazgier, V. (CZ) Berka, K. (CZ) Řezníčková, Eva (UEB-Q)_{RID, ORCID} Béres, T. (CZ) Strnad, Miroslav (UEB-Q)_{RID, ORCID} Kryštof, Vladimír (UEB-Q)_{RID, ORCID}
Source Title	Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623 Roč. 56, č. 15 (2013), s. 6234-6247
Number of pages	14 s.
Language	eng - English
Country	US - United States
Keywords	CHRONIC LYMPHOCYTIC-LEUKEMIA ; DINACICLIB SCH 727965 ; CELL-CYCLE
Subject RIV	ED - Physiology
R&D Projects	GAP305/12/0783 GA ČR - Czech Science Foundation (CSF)
	GD203/09/H046 GA ČR - Czech Science Foundation (CSF)
CEZ	AV0Z50380511 - UEB-Q (2005-2011)
UT WOS	000323082400018
DOI	10.1021/jm4006884
Annotation	The inhibition of overactive CDKs during cancer remains an important strategy in cancer drug development. We synthesized and screened a novel series of 2-substituted-6-biarylmethylamino-9-cyclopentylpurine derivatives for improved CDK inhibitory activity and antiproliferative effects. One of the most potent compounds, 6b, exhibited strong cytotoxicity in the human melanoma cell line G361 that correlated with robust CDK1 and CDK2 inhibition and caspase activation. In silico modeling of 6b in the active site of CDK2 revealed a high interaction energy, which we believe is due to the 6-heterobiarylmethylamino substitution of the purine moiety.
Workplace	Institute of Experimental Botany
Contact	David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469
Year of Publishing	2014

Number of the records: 1