Recent advances in the development of P2Y₁₄R inhibitors: a patent and literature review (2018-present)

ABSTRACT

Introduction

The P2Y₁₄ receptor (P2Y₁₄R), a member of the G protein-coupled receptor family, is activated by extracellular nucleotides. Due to its involvement in inflammatory, immunological and other associated processes, P2Y₁₄R has emerged as a promising therapeutic target. Despite lacking a determined three-dimensional crystal structure, the homology modeling technique based on closely related P2Y receptors’ crystallography has been extensively utilized for developing active compounds targeting P2Y₁₄R. Recent discoveries have unveiled numerous highly effective and subtype-specific P2Y₁₄R inhibitors. This study presents an overview of the latest advancements in P2Y₁₄R inhibitors.

Areas covered

This review presents an overview of the advancements in P2Y₁₄R inhibitor research over the past five years, encompassing new patents, journal articles, and highlighting the therapeutic prospects inherent in these compounds.

Expert opinion

The recent revelation of the vast potential of P2Y₁₄R inhibitors has led to the development of novel compounds that exhibit promising capabilities for the treatment of sterile inflammation of the kidney, potentially diabetes, and asthma. Despite being a relatively nascent class of compounds, certain members have already exhibited their capacity to surmount specific challenges posed by conventional P2Y₁₄R inhibitors. Targeting P2Y₁₄R through small molecules may present a promising therapeutic strategy for effectively managing diverse inflammatory diseases.

KEYWORDS:

• P2Y₁₄R
• Inhibitors
• Inflammatory diseases
• Virtual screening

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Article highlights:

• P2Y₁₄R has emerged as a promising drug target, particularly in the field of anti-inflammatory interventions.

• A panel of small-molecule inhibitors that target the P2Y₁₄R has been identified.

• The integration of more precise P2Y₁₄R structures with computational methodologies would accelerate the development of potent inhibitors possessing novel chemical scaffolds.

• A plethora of naturally occurring compounds, exhibiting a wide array of structures, holds great potential for discovering P2Y₁₄R inhibitors.

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.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Author Contributions

K Wang and F Zhong contributed equally to this work. The manuscript was written through the contributions of all authors. All authors have given approval to the final version of the manuscript.

Acknowledgments

We thank L Xu in the Institute of Bioinformatics and Medical Engineering at Jiangsu University of Technology for providing the Discovery Studio and Schrödinger software package to carry out molecular docking studies.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13543776.2024.2369634

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (Grant No. 82373725), the Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD) and Science and Technology Program of Suzhou (Grant No. SKY2023127; SKY2022103).