New Kinase Inhibitors That Are Selectively Cytotoxic for Tumor Cells

D A Skvortsov; I V Zhirkina; D A Ipatova; A R Pisarev; A S Malyshev; Y A Ivanenkov; V G Kartsev; O A Dontsova

doi:10.1134/S1607672924601446

New Kinase Inhibitors That Are Selectively Cytotoxic for Tumor Cells

Dokl Biochem Biophys. 2025 Apr;521(1):239-245. doi: 10.1134/S1607672924601446. Epub 2025 Apr 12.

Authors

D A Skvortsov¹, I V Zhirkina², D A Ipatova², A R Pisarev³, A S Malyshev^{4

5}, Y A Ivanenkov^{4

5}, V G Kartsev⁶, O A Dontsova^{2

7

8}

Affiliations

¹ Chemistry Department and Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia. skvorratd@mail.ru.
² Chemistry Department and Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
³ Faculty of Biology and Biotechnologies, Higher School of Economics, Moscow, Russia.
⁴ Hertsen Moscow Oncology Research Institute, Moscow, Russia.
⁵ Federal State Unitary Enterprise Dukhov Automatics Research Institute, Moscow, Russia.
⁶ InterBioScreen Ltd, Chernogolovka, Russia.
⁷ Skolkovo Institute of Science and Technology, Moscow, Russia.
⁸ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

Abstract

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.

Keywords: FCCT test; anticancer drugs; cytotoxicity; kinase inhibitors; selectivity.

MeSH terms

Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Cell Line, Tumor
Humans
MCF-7 Cells
PC-3 Cells
Protein Kinase Inhibitors* / chemistry
Protein Kinase Inhibitors* / pharmacology

Substances

Protein Kinase Inhibitors
Antineoplastic Agents