| OTYEPKA, Michal, Vladimír KRYŠTOF, Libor HAVLÍČEK, Věra SIEGLEROVÁ, Miroslav STRNAD a Jaroslav KOČA. Docking-Based Development of Purine-like Inhibitors of Cyclin-Dependent Kinase 2. Journal of Medicinal Chemistry. American Chemical Society, 2000, roč. 43, č. 13, s. 2506-2513. ISSN 0022-2623. |
Další formáty:
BibTeX
LaTeX
RIS
@article{350391,
author = {Otyepka, Michal and Kryštof, Vladimír and Havlíček, Libor and Sieglerová, Věra and Strnad, Miroslav and Koča, Jaroslav},
article_number = {13},
language = {eng},
issn = {0022-2623},
journal = {Journal of Medicinal Chemistry},
title = {Docking-Based Development of Purine-like Inhibitors of Cyclin-Dependent Kinase 2},
volume = {43},
year = {2000}
}
TY - JOUR
ID - 350391
AU - Otyepka, Michal - Kryštof, Vladimír - Havlíček, Libor - Sieglerová, Věra - Strnad, Miroslav - Koča, Jaroslav
PY - 2000
TI - Docking-Based Development of Purine-like Inhibitors of Cyclin-Dependent Kinase 2
JF - Journal of Medicinal Chemistry
VL - 43
IS - 13
SP - 2506
EP - 2506
PB - American Chemical Society
SN - 00222623
N2 - The cell division cycle is controlled by cyclin-dependent kinases (cdk), which consist of a catalytic subunit (cdk1-cdk8) and a regulatory subunit (cyclin A-H). Purine-like inhibitors of cyclin-dependent kinases have recently been found to be of potential use as anticancer drugs. Rigid and flexible docking techniques were used for analysis of binding mode and design of new inhibitors. X-ray structures of three (ATP, olomoucine, roscovitine) cdk2 complexes were available at the beginning of the study and were used to optimize the docking parameters. The new potential inhibitors were then docked into the cdk2 enzyme, and the enzyme/inhibitor interaction energies were calculated and tested against the assayed activities of cdk1 (37 compounds) and cdk2 (9 compounds). A significant rank correlation between the activity and the rigid docking interaction energy has been found. This implies that (i) the rigid docking can be used as a tool for qualitative prediction of activity and (ii) values obtained by the rigid docking technique into the cdk2 active site can also be used for the prediction of cdk1 activity. While the resulting geometries obtained by the rigid docking are in good agreement with the X-ray data, the flexible docking did not always produce the same inhibitor conformation as that found in the crystal.
ER -
OTYEPKA, Michal, Vladimír KRYŠTOF, Libor HAVLÍČEK, Věra SIEGLEROVÁ, Miroslav STRNAD a Jaroslav KOČA. Docking-Based Development of Purine-like Inhibitors of Cyclin-Dependent Kinase 2. \textit{Journal of Medicinal Chemistry}. American Chemical Society, 2000, roč.~43, č.~13, s.~2506-2513. ISSN~0022-2623.
|
