A patent review of ubiquitin-specific protease 7 (USP7) inhibitors (2014-present)

ABSTRACT

Introduction

Ubiquitin-specific protease 7 (USP7) plays a critical role in multiple signaling pathways, and many recent studies have proved its association with many diseases. The USP7-murine double minute 2-p53 pathway and the relationship between USP7 and the important immune protein PD-L1 in cancer progression and metastasis have been clarified. Recently, USP7 has emerged as a promising and potent therapeutic target for cancer and has attracted both academic and industrial attention.

Areas covered

This review focuses on the structure, activity, and applications of USP7 inhibitors in cancer therapy. It also focuses on patents reported since 2014.

Expert opinion

Recently, USP7 has attracted considerable attention owing to its physiological and pathophysiological roles in cancer progression, and few studies have focused on the development of USP7 inhibitors. Compared with micromolar first-generation USP7 inhibitors, second-generation USP7 inhibitors exhibit higher potency (at nanomolar level for both USP7 and cell inhibitory activities), higher selectivity, and better pharmacokinetic properties, and they largely broaden the range of candidates for further clinical tests. However, there is still a need for a more precise description of compounds with receptors, the structural diversity of these compounds, and screening methods.

KEYWORDS:

• Application
• cancer
• inhibitors
• patent
• ubiquitin-specific protease 7

Article highlights

• Ubiquitin-specific protease 7 (USP7) plays an important role in multiple cellular pathways and has emerged as a biomarker and promising drug target.

• USP7-related diseases are well studied, especially cancer- and immune-related diseases.

• USP7 inhibitor patents ranging from 2014 to date, their structures, activities, and applications in disease therapy are reviewed and summarized.

• USP7 applications in the diagnosis and treatment of disease are summarized.

This box summarizes key points contained in the article.

Declarations of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81773562, 82020108030, and U1904163), National Key Research and Development Project (No. 2018YFE0195100, China), and the Science and Technology Program of Henan Province (No. 202102310152, China).