Fezagepras (developmental code name PBI-4050), also known previously as setogepram, is an experimental drug which acts as a mixed agonist-antagonist for certain free fatty acid receptors, being an agonist at FFAR1 (GPR40) but an antagonist at GPR84. It has antiinflammatory and anti-fibrotic effects and has reached Phase II human clinical trials for treatment of idiopathic pulmonary fibrosis. However, development was discontinued for all indications in 2022. Medium-chain fatty acids are known to act as GPR84 agonists and have been found to produce inflammation and mediate aging-associated cognitive decline via this action. Fezagepras has been found to block 3-hydroxyoctanoic acid (3-HOA)-mediated neuronal inhibition in the hippocampus and associated cognitive impairment in rodents. Similarly, it blocked the detrimental effects of the medium-chain fatty acid-producing gut bacteria Parabacteroides goldsteinii on memory in rodents. In addition, fezagepras restored youthful memory function in aged rodents.
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