Protein tyrosine phosphatase inhibitors: a patent review and update (2012–2023)

ABSTRACT

Introduction

Protein tyrosine phosphatases (PTPs), essential and evolutionarily highly conserved enzymes, govern cellular functions by modulating tyrosine phosphorylation, a pivotal post-translational modification for signal transduction. The recent strides in phosphatase drug discovery, leading to the identification of selective modulators for enzymes, restoring interest in the therapeutic targeting of protein phosphatases.

Areas covered

The compilation of patents up to the year 2023 focuses on the efficacy of various classes of Tyrosine phosphatases and their inhibitors, detailing their chemical structure and biochemical characteristics. These findings have broad implications, as they can be applied to treating diverse conditions like cancer, diabetes, autoimmune disorders, and neurological diseases. The search for scientific articles and patent literature was conducted using well known different platforms to gather information up to 2023.

Expert opinion

The latest improvements in protein tyrosine phosphatase (PTP) research include the discovery of new inhibitors targeting specific PTP enzymes, with a focus on developing allosteric site covalent inhibitors for enhanced efficacy and specificity. These advancements have not only opened up new possibilities for therapeutic interventions in various disease conditions but also hold the potential for innovative treatments. PTPs offer promising avenues for drug discovery efforts and innovative treatments across a spectrum of health conditions.

KEYWORDS:

• Patents
• PTPs
• active site
• drug discovery
• diabetes

Article highlights

• Protein tyrosine phosphatases (PTPs) are essential enzymes that regulate cellular functions by modulating tyrosine phosphorylation, a key post-translational modification for signal transduction.

• Potent drugs like SHP09936 and TNO15537, which are allosteric inhibitors of SHP2 and compound, GP03 stands out with an IC50 of 2.89 μM against phosphatase receptor type O (PTPRO), demonstrating specificity toward other protein phosphatases.

• Mechanisms of binding for both active site inhibitors like TCS40 and allosteric inhibitors such as benzofuran compounds, emphasizing the importance of hydrogen bonds in maintaining structural integrity.

• The role of computational methods in complementing experimental approaches to design PTP inhibitors, enhancing the understanding of binding mechanisms and aiding in the development of effective inhibitors

• Significant advances made in discovering novel protein tyrosine phosphatase (PTP) inhibitors from 2012 to 2023, showcasing contributions from various pharmaceutical companies and research groups.

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 material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

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

Author contributions

All authors contributed equally. Ms. LMK was responsible for the conceptualization, data curation, and drafting of the original manuscript. Ms.VC, SD, DK contributed to the methodology, validation, and formal analysis. All authors read and approved the final manuscript.

Additional information

Funding

This paper was funded by the Department of Biotechnology (DBT), New Delhi (grant no. BT/PR140164).