New Kinase Inhibitors That Are Selectively Cytotoxic for Tumor Cells
To search for substances selectively acting on tumor cells, phenotypic screening in a coculture of tumor cells with non-tumor cells was used in the work. The compound STOCK7S-36520, selectively cytotoxic in the coculture of breast tumor cells MCF7' and non-tumor MCF10A cells, contains structural elements characteristic of kinase inhibitors. Analysis of the compound STOCK7S-36520 and its derivative STOCK7S-47016 showed that they are new multikinase inhibitors. The highest inhibition of 84% was shown by compound STOCK7S-47016 against GCK kinase. Of interest is the significant selectivity of action against some of the cell lines studied: the selectivity index of STOCK7S-36520 against the prostate tumor cell line PC3 is 29 times compared to the model line of non-tumor fibroblasts VA13.
Authors
- Dmitry A. Skvortsov (ORCID: https://orcid.org/0000-0001-8336-8596)
- Olga А. Dontsova (ORCID: https://orcid.org/0000-0002-0040-2662)
- А. А. Писарев (ORCID: https://orcid.org/0000-0003-0017-1478)
- Irina V. Zhirkina (ORCID: https://orcid.org/0000-0002-1927-1850)
- Yan A. Ivanenkov (ORCID: https://orcid.org/0000-0002-8968-0879)
- Daria A. Ipatova
- В. Г. Карцев
- А. В. Малышев (ORCID: https://orcid.org/0000-0002-5308-1698)
Institutions
- National Research University Higher School of Economics (RU)
- Skolkovo Institute of Science and Technology (RU)
- Lomonosov Moscow State University (RU)
- Institute of Bioorganic Chemistry (RU)
- All Russia Research Institute of Automatics (RU)
- Scientific Center of RAS in Chernogolovka (RU)
- P.A. Hertzen Moscow Oncology Research Institute (RU)
Publication Details
- Journal
- Doklady Biochemistry and Biophysics
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1134/s1607672924601446
- Primary Topic
- Computational Drug Discovery Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Institut National de la Santé et de la Recherche Médicale
- Russian Science Foundation