AI Article Synopsis
- The free fatty acid receptor 2 (FFA2/GPR43) is linked to short-chain fatty acids and is a potential target for treating metabolic and inflammatory diseases.
- Researchers conducted bioisosteric replacements on the carboxylic acid group of the FFA2 antagonist CATPB, leading to new compounds.
- TUG-2304 emerged as a high-potency antagonist with impressive activity in tests, showing the ability to fully inhibit neutrophil migration and respiratory bursts triggered by propionate.
Article Abstract
The free fatty acid receptor 2 (FFA2), also known as GPR43, mediates effects of short-chain fatty acids and has attracted interest as a potential target for treatment of various metabolic and inflammatory diseases. Herein, we report the results from bioisosteric replacement of the carboxylic acid group of the established FFA2 antagonist CATPB and SAR investigations around these compounds, leading to the discovery of the first high-potency FFA2 antagonists, with the preferred compound TUG-2304 () featuring IC values of 3-4 nM in both cAMP and GTPγS assays, favorable physicochemical and pharmacokinetic properties, and the ability to completely inhibit propionate-induced neutrophil migration and respiratory burst.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10547238 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.2c01935 | DOI Listing |
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