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

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

Журнал

Cancers
ISSN: 2072-6694

Вых. Данные

Год: 2023, Том: 15, Номер: 15, Номер статьи : 3766, Страниц : DOI: 10.3390/cancers15153766

Авторы

Rusina Polina ¹ , Gandalipov Erik ^2,3 , Abdusheva Yana ^4,3,1 , Panova Maria ^3,1 , Burdenkova Alexandra ^4,1 , Chaliy Vasiliy ¹ , Brachs Maria ⁵ , Stroganov Oleg ⁶ , Guzeeva Ksenia ⁴ , Svitanko Igor ^4,1 , Shtil Alexander ^7,8 , Novikov Fedor ^4,3,1

Организации

1	Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Avenue, 119991 Moscow, Russia
2	Laboratory of Solution Chemistry and Advanced Materials Technologies, ITMO University, 9 Lomonosov Street, 191002 Saint-Petersburg, Russia
3	PHARMENTERPRISES LLC, Skolkovo Innovation Center, 42 (1) Bolshoi Blvd., 143026 Moscow, Russia
4	Higher School of Economics, National Research University, 20 Myasnitskaya Street, 101000 Moscow, Russia
5	Treamid Therapeutics GmbH, c/o CoLaborator (Bayer), Building S141, Muellerstraβe 178, 13353 Berlin, Germany
6	BioMolTech Corp., Toronto, ON M2L 1L1, Canada
7	Blokhin National Medical Research Center of Oncology, 24 Kashirskoye Shosse, 115522 Moscow, Russia
8	Institute of Cyber Intelligence Systems, National Research Nuclear University MEPhI, 31 Kashirskoye Shosse, 115409 Moscow, Russia

General toxicity for the organism is a major drawback of anticancer drugs. Development of new generation chemotherapeutics requires the knowledge about macromolecules critical for tumor cell viability. Among these species (called therapeutic targets), the protein kinases are the established enzymes. However, the parts of protein kinases that are supposed to be targeted by drugs can be structurally similar. Therefore, it is difficult to design the compounds that selectively bind and inactivate individual kinases, especially if the proteins comprise the evolutionarily conserved families. In the present study, a set of advanced approaches of computational chemistry and biochemistry was used for the structure-based design of new compounds to inhibit cyclin-dependent protein kinases (CDK), the enzymes mechanistically implicated in tumor biology. We demonstrated the advantages of the non-equilibrium (NEQ) thermodynamics method for a time-efficacious, accurate, and informative prediction of CDK inhibitory properties of new compounds. Importantly, NEQ-based predictions correlated with experimental testing.

Rusina P. , Gandalipov E. , Abdusheva Y. , Panova M. , Burdenkova A. , Chaliy V. , Brachs M. , Stroganov O. , Guzeeva K. , Svitanko I. , Shtil A. , Novikov F.
Imidazole-4-N-acetamide Derivatives as a Novel Scaffold for Selective Targeting of Cyclin Dependent Kinases
Cancers. 2023. V.15. N15. 3766 . DOI: 10.3390/cancers15153766 WOS Scopus OpenAlex

Web of science:	WOS:001045383600001
Scopus:	2-s2.0-85167798418
OpenAlex:	W4385278170

БД	Цитирований
OpenAlex	6
Scopus	4
Web of science	4