A patent review of PRMT5 inhibitors to treat cancer (2018 - present)

ABSTRACT

Introduction

Protein arginine methyltransferase 5 (PRMT5) belongs to type II arginine methyltransferases. Since PRMT5 plays an essential role in mammalian cells, it can regulate various physiological functions, including cell growth and differentiation, DNA damage repair, and cell signal transduction. It is an epigenetic target with significant clinical potential and may become a powerful drug target for treating cancers and other diseases.

Areas covered

This review provides an overview of small-molecule inhibitors and their associated combined treatment strategies targeting PRMT5 in cancer treatment patents published since 2018, and also summarizes the progress made by several biopharmaceutical companies in the development, application, and clinical trials of small-molecule PRMT5 inhibitors. The data in this review come from WIPO, UniProt, PubChem, RCSB PDB, National Cancer Institute, and so on.

Expert opinion

Many PRMT5 inhibitors have been developed with good inhibitory activities, but most of them lack selectivities and are associated with adverse clinical responses. In addition, the progress was almost all based on the previously established skeleton, and more research and development of a new skeleton still needs to be done. The development of PRMT5 inhibitors with high activities and selectivities is still an essential aspect of research in recent years.

KEYWORDS:

• PRMT5
• inhibitor
• epigenetic target
• cancer treatment
• combined treatment

Article highlights

• PRMT5 may participate in the pathogenesis of colorectal cancer by regulating oncogenes at the epigenetic level, and tumor drugs targeting PRMT5 have an ample development space and prospects.

• Abstracts of patent literature describing the development of PRMT5 inhibitors classified by companies between 2018 and 2023 are provided, highlighting their structures and activities.

• This article mentions compounds currently in clinical trials and lists first-in-class PRMT5 degrader (MS4322).

This box summarizes key points contained in the article.

Declaration 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.

Author contributions

J Gao, J Yang and S Xue contributed equally to this work. H Lin and C Luo conceived the ideas and instructed the writing. S Xue instructed the section related to biology. J Gao, J Yang, S Xue and H. Lin drafted the manuscript. J Gao, J Yang and S Xue collected the references and clinical trial information in this field.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was funded by the National Centre for Protein Science Shanghai (Protein Expression and Purification system), the National Key R&D Program of China [2022YFC3400500 and 2021ZD0203900 to C.L.], Fujian Provincial Natural Science Foundation [2021J01203 to H.L.], the National Natural Science Foundation of China [91853205, 81821005, 92253303 to C.L.], the project of National Multidisciplinary Innovation Team of Traditional Chinese Medicine supported by National Administration of Traditional Chinese Medicine [ZYYCXTD-202004 to C.L.], High-level new R&D institute [2019B090904008 to C.L.], High-level Innovative Research Institute [2021B0909050003 to C.L.], Department of Science and Technology of Guangdong Province.