Generation and validation of a high-throughput screening system for the identification of eIF4F inhibitors with anti-melanoma activity

Kód projektu
MUNI/11/ACC/2/2022
Období řešení
1/2022 - 12/2023
Investor / Programový rámec / typ projektu
Masarykova univerzita
Fakulta / Pracoviště MU
Lékařská fakulta

High-throughput drug screening platforms utilize robotic microplate manipulation, automated liquid handling, data acquisition, and analysis to rapidly screen thousands of chemical compounds. Pharmaceutical companies use them to identify compounds with desired biological activity that could lead to new therapies. We will develop and test a new rapid screening system for the high-throughput identification and characterization of small-molecule inhibitors of the translation initiation complex eIF4F, identified as a potential therapeutic target in many human cancers, including drug-resistant malignant melanoma. The current portfolio of eIF4F inhibitors is limited, and none of the compounds has entered the clinical evaluation phase. It is caused, at least in part, by the fact that the state-of-the-art approaches for eIF4F inhibitor identification and characterization are based on techniques that are costly, time-consuming, or rely on expensive equipment for automated image analysis. In contrast, our novel approach, based on a recent identification by our group of previously unknown eIF4F targets, will overcome most limitations of the currently used techniques. Our unique know-how will allow us to develop a new cell-based system better suited for the high-throughput screening (HTS) of chemical libraries for compounds targeting eIF4F than the currently available screening systems.

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