PROTAC: targeted drug strategy. Principles and limitations

Koroleva, OA; Dutikova, YV; Trubnikov, AV; Zenov, FA; Manasova, EV; Shtil, AA; Kurkin, AV

Abstract

The PROTAC (PROteolysis TArgeting Chimera) technology is a method of targeting intracellular proteins previously considered undruggable. This technology utilizes the ubiquitin-proteasome system in cells to specifically degrade target proteins, thereby offering significant advantages over conventional small-molecule inhibitors of the enzymatic function. Preclinical and preliminary clinical trials of PROTAC-based compounds (degraders) are presented. The review considers the general principles of the design of degraders. Advances and challenges of the PROTAC technology are discussed.

Keywords: PROTAC technology; proteolysis; cancer therapy

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