An updated patent review of GPR40/ FFAR1 modulators (2020 – present)

ABSTRACT

Introduction

Free fatty acid receptor 1 (FFAR1) is a potential therapeutic target for type 2 diabetes mellitus (T2DM) because it could clinically stimulate insulin release in a glucose-dependent manner without inducing hypoglycemia. In both the pharmaceutical industry and academic community, FFAR1 agonists have attracted considerable attention.

Areas covered

The review presents a patent overview of FFAR1 modulators in 2020–2023, along with chemical structures, the biological activities and therapeutic applications of the representative compounds. Our patent survey used the major electronic databases, namely SciFinder, and Web of Science and Innojoy.

Expert opinion

Although FFAR1 agonists exhibit outstanding advantages, they are also associated with significant challenges. At present, reducing the molecular weight and overall lipophilicity and developing tissue-specific FFAR1 agonists may be the strategies for alleviating hepatotoxicity.

KEYWORDS:

• Free fatty acid receptor 1
• type 2 diabetes
• hypoglycemia
• glucose-stimulated insulin secretion
• agonist

Article highlights

• The review covers the recent progress (2020–present) in the patent applications of FFAR1 modulators, along with chemical structures, the biological activities and therapeutic applications of the representative compounds.

• The review summarizes FFAR1 modulators in active clinical trials, and counts the annual publication volume related to FFAR1 between 2002 and 2023.

• Reducing the molecular weight and overall lipophilicity and developing tissue-specific modulators may be the strategies for alleviating hepatotoxicity of FFAR1 modulators.

• Significant challenges remain to explore new indications and clarify the mechanism of hepatotoxicity.

Declaration of interests

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 contribution statement

Hai Qian and Wei Shi conceptualized and designed this review. Qiang Ren and Yiqing Fan collected data and drafted manuscripts. Qiang Ren, Yiqing Fan, Lixin Yang , Mayu Shan, Wei Shi and Hai Qian revised the manuscript critically for important intellectual content.

Additional information

Funding

This paper was funded by the National Natural Science Foundation of China [Nos. 81872734 & 82204195], and the China Postdoctoral Science Foundation[No. 2020M681792].