Peroxisome Proliferator-Activated Receptor agonists and antagonists: an updated patent review (2020–2023)

ABSTRACT

Introduction

The search for novel compounds targeting Peroxisome Proliferator-Activated Receptors (PPARs) is currently ongoing, starting from the previous successfully identification of selective, dual or pan agonists. In last years, researchers’ efforts are mainly paid to the discovery of PPARγ and δ modulators, both agonists and antagonists, selective or with a dual-multitarget profile. Some of these compounds are currently under clinical trials for the treatment of primary biliary cirrhosis, nonalcoholic fatty liver disease, hepatic, and renal diseases.

Areas covered

A critical analysis of patents deposited in the range 2020–2023 was carried out. The novel compounds discovered were classified as selective PPAR modulators, dual and multitarget PPAR agonists. The use of PPAR ligands in combination with other drugs was also discussed, together with novel therapeutic indications proposed for them.

Expert opinion

From the analysis of the patent literature, the current emerging landscape sees the necessity to obtain PPAR multitarget compounds, with a balanced potency on three subtypes and the ability to modulate different targets. This multitarget action holds great promise as a novel approach to complex disorders, as metabolic, inflammatory diseases, and cancer. The utility of PPAR ligands in the immunotherapy field also opens an innovative scenario, that could deserve further applications.

KEYWORDS:

• Dual agonists
• immunotherapy
• modulators
• multitarget PPAR agonist
• MASLD
• MASH
• PPAR

Article highlights

• The status on the clinical development of PPAR drugs is presented.

• Newly synthesized molecules are proposed as selective, dual and pan PPAR agonists.

• Multitarget PPAR/FFAR1 agonists open the way to novel treatment options in metabolic disorders.

• Combination treatments and novel therapeutic indications for PPAR drugs are discussed.

• Cancer immunotherapy represents an innovative field of application of PPAR drugs.

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.

Authors contribution statement

A. Ammazzalorso and B. De Filippis searched for the literature. A. Granese filtered the search results. All the authors analyzed the data. A. Ammazzalorso wrote the manuscript. All the authors read and approved the final version of the manuscript.

Additional information

Funding

This paper was not funded.