Recent Progress of Ubiquitin-Specific-Processing Protease 7 Inhibitors

The ubiquitination process refers to the classification of intracellular proteins by ubiquitin molecules under the action of a series of special enzymes (ubiquitin-activating enzymes, ligases, conjugating enzymes, etc.), and selecting target protein molecules for specific modification. The process of ubiquitination indicates that ubiquitination plays an important role in protein localization, metabolism, regulation, and degradation. At present, the development of novel, high-efficiency, and specific USP7 small-molecule inhibitors and the research on the mechanism of action of these inhibitors to specifically recognize the USP7 enzyme are low in fuel. In this review, the activation process of deubiquitinase USP7 is elaborated, and the small molecule inhibitors are divided into three sites of action according to the different sites of action in the catalytic domain of USP7 and the mechanism of these small molecule compounds inhibiting the activation process of USP7 are dissected. At the same time, the full-length structure of USP7 and the design strategy of representative USP7 inhibitors are briefly described. In addition, we summarize the characteristics of the spatial structure and mechanism of action of each action site and discuss the limiting factors of USP7 inhibitor development. This review may promote small-molecule compounds to generate novel high-efficiency and specific USP7 inhibitors based on backbone structure modification.