Pyrimidine-based pyrazoles as cyclin-dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00493391" target="_blank" >RIV/61388963:_____/18:00493391 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1111/cbdd.13334" target="_blank" >http://dx.doi.org/10.1111/cbdd.13334</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/cbdd.13334" target="_blank" >10.1111/cbdd.13334</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pyrimidine-based pyrazoles as cyclin-dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation

Popis výsledku v původním jazyce

A series of new pyrimidine-pyrazole hybrid molecules were designed as inhibitors of cyclin-dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2-CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50<20nm), which can be further optimized to have selectivity over other kinase isoforms.

Název v anglickém jazyce

Pyrimidine-based pyrazoles as cyclin-dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation

Popis výsledku anglicky

A series of new pyrimidine-pyrazole hybrid molecules were designed as inhibitors of cyclin-dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2-CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50<20nm), which can be further optimized to have selectivity over other kinase isoforms.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemical Biology & Drug Design

ISSN

1747-0277

e-ISSN

—

Svazek periodika

92

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

1683-1691

Kód UT WoS článku

000443302700010

EID výsledku v databázi Scopus

2-s2.0-85052550577