Recent advances in the development of ubiquitin-specific-processing protease 7 (USP7) inhibitors

Abstract

Ubiquitin-specific-processing protease 7 (USP7) is one among the several deubiquitinating enzymes gaining central attention in the current cancer research. Most recent studies have focused on illustrating how USP7 is involved in the cancer process, while few articles reported the development of small molecule USP7 inhibitors. Although some review articles dealt with USP7, they mainly focused on its physiological role and not on the development of USP7 inhibitors. In this review, we systematically summarise the structures, activities and structure-activity relationship (SAR) of small molecule USP7 inhibitors, recently disclosed in scientific articles and patents from 2000 to 2019. The binding modes of typical compounds and their interactions with USP7 are also presented, while other deubiquitinase inhibitors are described in detail. Meanwhile, we briefly introduce the biochemical and physiological functions of USP7. Finally, challenges and potential strategies in developing small molecule USP7 inhibitors are also discussed.

Keywords: Cancer; Inhibitors; SAR; USP7; Ubiquitination.