Targeting the relaxin-3/RXFP3 system: a patent review for the last two decades

ABSTRACT

Introduction

The neuropeptide relaxin-3/RXFP3 system belongs to the relaxin/insulin superfamily and is involved in many important physiological processes, such as stress responses, appetite control, and motivation for reward. Although relaxin-3 is the endogenous agonist for RXFP3, it can also bind to and activate RXFP1 and RXFP4. Consequently, research has been focused on the development of RXFP3-specific peptides and small-molecule ligands to validate the relaxin-3/RXFP3 system as a novel drug target.

Areas covered

This review provides an overview of patents on the relaxin-3/RXFP3 system covering ligand development and pharmacological studies since 2003. Related patents and literature reports were obtained from established sources including SciFinder, Google Patents, and Espacenet for patents and SciFinder, PubMed, and Google Scholar for literature reports.

Expert opinion

There has been an increasing amount of patent activities around relaxin-3/RXFP3, highlighting the importance of this novel neuropeptide system for drug discovery. The development of relaxin-3 derived peptides and small-molecule modulators, as well as behavioral studies in rodents, have shown that the relaxin-3/RXFP3 system is a promising drug target for treating various metabolic and neuropsychiatric diseases including obesity, anxiety, and alcohol addiction.

KEYWORDS:

• Relaxin-3
• RXFP3
• agonists
• antagonists
• allosteric modulators

Article highlights

• This review is focused on patents with claims for the relaxin-3/RXFP3 system since 2003.

• Several diseases including obesity, diabetes, anxiety, and alcohol addiction are linked to the relaxin-3/RXFP3 system.

• Peptide modulators have undergone majority of the innovation while small-molecule modulators began to surface lately.

• Synthesis and availability of peptide modulators remain challenging and simplified single-chain peptide derivatives have been developed.

• Selectivity among receptor subtypes, oral bioavailability, and in vivo stability of peptide modulator are major challenges.

Declaration of interests

Chunyang Jin is employed by the Research Triangle Institute and is a co-inventor on a patent application for RXFP3 antagonists (WO2022192126A1). The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Author contribution statement

MTR, HHCL, JH, and CJ contributed to writing this manuscript. MTR led writing the first draft. CJ conceptualized and led the project. All authors have given approval to the final version of the manuscript.

Additional information

Funding

This paper was funded by the research grants R01AA028255 and R01AA026820 to Chunyang Jin from the National Institute on Alcohol Abuse and Alcoholism, the National Institutes of Health.