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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 main pharmacokinetic parameters of a new stimulator of cognitive brain functions, OSPL – 502 have been determined: area under the concentration-time curve, elimination rate constant, half-elimination period, time to reach the maximum concentration, maximum concentration, volume distribution, total clearance and bioavailability of the dosage form. The main metabolites of the active substance of the dosage form of the new stimulator of cognitive functions OSPL – 502 have been analyzed. The data obtained predict the effects of the drug in humans relevant for further clinical investigation.