Publication:
Imidazole-4-N-acetamide Derivatives as a Novel Scaffold for Selective Targeting of Cyclin Dependent Kinases

Файлы
W4385278170.pdf(1.83 MB)
Дата
2023
Авторы
Rusina, P.
Gandalipov, E.
Abdusheva, Y.
Panova, M.
Shtil, A.
Journal Title
Journal ISSN
Volume Title
Издатель
Научные группы
Организационные подразделения
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Организационная единица
Институт интеллектуальных кибернетических систем
Цель ИИКС и стратегия развития - это подготовка кадров, способных противостоять современным угрозам и вызовам, обладающих знаниями и компетенциями в области кибернетики, информационной и финансовой безопасности для решения задач разработки базового программного обеспечения, повышения защищенности критически важных информационных систем и противодействия отмыванию денег, полученных преступным путем, и финансированию терроризма.
Выпуск журнала
Аннотация
The rational design of cyclin-dependent protein kinase (CDK) inhibitors presumes the development of approaches for accurate prediction of selectivity and the activity of small molecular weight anticancer drug candidates. Aiming at attenuation of general toxicity of low selectivity compounds, we herein explored the new chemotype of imidazole-4-N-acetamide substituted derivatives of the pan-CDK inhibitor PHA-793887. Newly synthesized compounds 1-4 containing an aliphatic methyl group or aromatic radicals at the periphery of the scaffold were analyzed for the prediction of relative free energies of binding to CDK1, -2, -5, and -9 using a protocol based on non-equilibrium (NEQ) thermodynamics. This methodology allows for the demonstration of a good correlation between the calculated parameters of interaction of 1-4 with individual targets and the values of inhibitory potencies in in vitro kinase assays. We provide evidence in support of NEQ thermodynamics as a time sparing, precise, and productive approach for generating chemical inhibitors of clinically relevant anticancer targets.
Описание
Ключевые слова
Acetamide , Imidazole , Drug Target Identification , Cancer Therapy , Drug design , Rational design , Kinome
Цитирование
Imidazole-4-N-acetamide Derivatives as a Novel Scaffold for Selective Targeting of Cyclin Dependent Kinases / Rusina, P. [et al.] // Cancers. - 2023. - 15. - № 15. - 10.3390/cancers15153766
URI
https://www.doi.org/10.3390/cancers15153766
 https://www.scopus.com/record/display.uri?eid=2-s2.0-85167798418&origin=resultslist
 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:001045383600001
 https://openrepository.mephi.ru/handle/123456789/29180
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