E3S Web of Conf.
Volume 215, 2020International Scientific Conference on Biotechnology and Food Technology (BFT-2020)
|Number of page(s)||6|
|Section||Biomedical Technology and Biopharmaceuticals|
|Published online||02 December 2020|
Treatment of chemoresistant cell lines with indolinone-based small molecules
St. Petersburg state institute of technology (technical univercity), Laboratory of molecular pharmacology, Moskovskii pr, 26, St. Petersburg, Russia
* Corresponding author: email@example.com
Reduced delivery of the drug into the cell due to increased activity of specific transporter P-glycoprotein is one of the main mechanisms of drug resistance development. The inhibition of the activity of such a pump increases the intracellular concentration of the drug and contributes to cancer cell death. The combination of factors that allows one to overcome genetically determined resistance and to trigger apoptosis in one small molecule compound can lead to the development of new type of drugs for personalized therapy of chemoresistant tumors. In the course of work on optimization of MDM2 inhibitors based on indolinones and isoindolinones, we found fragments of the structure that can be modified with minimal risk of a decrease in the target activity. The combination of in silico and in vitro methods allowed the selection of compounds that showed strong binding to the target sites of P-glycoprotein and MDM2, and a good combination of solubility - membrane-active properties, which implies high bioavailability of the drug.
© The Authors, published by EDP Sciences, 2020
This is an Open Access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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