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

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dc.contributor.authorRusina, P.
dc.contributor.authorGandalipov, E.
dc.contributor.authorAbdusheva, Y.
dc.contributor.authorPanova, M.
dc.contributor.authorShtil, A.
dc.contributor.authorШтиль, Александр Альбертович
dc.date.accessioned2024-12-27T09:06:54Z
dc.date.available2024-12-27T09:06:54Z
dc.date.issued2023
dc.description.abstractThe 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.
dc.identifier.citationImidazole-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
dc.identifier.doi10.3390/cancers15153766
dc.identifier.urihttps://www.doi.org/10.3390/cancers15153766
dc.identifier.urihttps://www.scopus.com/record/display.uri?eid=2-s2.0-85167798418&origin=resultslist
dc.identifier.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:001045383600001
dc.identifier.urihttps://openrepository.mephi.ru/handle/123456789/29180
dc.relation.ispartofCancers
dc.subjectAcetamide
dc.subjectImidazole
dc.subjectDrug Target Identification
dc.subjectCancer Therapy
dc.subjectDrug design
dc.subjectRational design
dc.subjectKinome
dc.titleImidazole-4-N-acetamide Derivatives as a Novel Scaffold for Selective Targeting of Cyclin Dependent Kinases
dc.typeArticle
dspace.entity.typePublication
oaire.citation.issue15
oaire.citation.volume15
relation.isAuthorOfPublicationd2e4a764-d93d-47f5-a8bc-09f718b121f7
relation.isAuthorOfPublication.latestForDiscoveryd2e4a764-d93d-47f5-a8bc-09f718b121f7
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