Number of the records: 1
Optimization of norbornyl-based carbocyclic nucleoside analogs as cyclin-dependent kinase 2 inhibitors
- 1.
SYSNO ASEP 0523373 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Optimization of norbornyl-based carbocyclic nucleoside analogs as cyclin-dependent kinase 2 inhibitors Author(s) Köprülüoglu, Cemal (UOCHB-X) ORCID, RID
Dejmek, Milan (UOCHB-X) RID, ORCID
Šála, Michal (UOCHB-X) RID, ORCID
Ajani, Haresh (UOCHB-X) ORCID, RID
Hřebabecký, Hubert (UOCHB-X) RID, ORCID
Fanfrlík, Jindřich (UOCHB-X) RID, ORCID
Jorda, Radek (UEB-Q) ORCID, RID
Dračínský, Martin (UOCHB-X) RID, ORCID
Procházková, Eliška (UOCHB-X) RID, ORCID
Šácha, Pavel (UOCHB-X) RID, ORCID
Kryštof, Vladimír (UEB-Q) RID, ORCID
Hobza, Pavel (UOCHB-X) RID, ORCID
Lepšík, Martin (UOCHB-X) RID, ORCID
Nencka, Radim (UOCHB-X) RID, ORCIDArticle number e2842 Source Title Journal of Molecular Recognition. - : Wiley - ISSN 0952-3499
Roč. 33, č. 8 (2020)Number of pages 16 s. Language eng - English Country GB - United Kingdom Keywords ATP-competitive type I inhibitors ; cyclin-dependent kinase 2 ; protein-ligand binding ; quantum mechanical scoring Subject RIV CF - Physical ; Theoretical Chemistry OECD category Physical chemistry R&D Projects EF16_019/0000729 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support UOCHB-X - RVO:61388963 ; UEB-Q - RVO:61389030 UT WOS 000549952000002 EID SCOPUS 85082200932 DOI 10.1002/jmr.2842 Annotation We report on the discovery of norbornyl moiety as a novel structural motif for cyclin‐dependent kinase 2 (CDK2) inhibitors which was identified by screening a carbocyclic nucleoside analogue library. Three micromolar hits were expanded by the use of medicinal chemistry methods into a series of 16 novel compounds. They had prevailingly micromolar activities against CDK2 and the best compound of the series attained IC50 of 190 nM. The binding modes were explored in molecular details by modeling and docking. Quantum mechanics‐based scoring was used to rationalize the affinities. In conclusion, the discovered 9‐hydroxymethylnorbornyl moiety was shown by joint experimental‐theoretical efforts to be able to serve as a novel substituent for CDK2 inhibitors. This finding opens door to the exploration of chemical space towards more effective derivatives targeting this important class of protein kinases. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2021 Electronic address https://onlinelibrary.wiley.com/doi/abs/10.1002/jmr.2842
Number of the records: 1