// Workers AI · dad joke modeWhat did Fezagepras say when it ran into an old friend? "It's been a fez-tastic day!
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| Other names | Setogepram; PBI-4050; PBI4050 |
| Drug class | FFAR1 (GPR40) agonist; GPR84 antagonist |
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| Formula | C13H18O2 |
| Molar mass | 206.285 g·mol−1 |
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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.[1] It has antiinflammatory and anti-fibrotic effects and has reached Phase II human clinical trials for treatment of idiopathic pulmonary fibrosis.[2][3][4][5][6] However, development was discontinued for all indications in 2022.[1]
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.[7][8][9] Fezagepras has been found to block 3-hydroxyoctanoic acid (3-HOA)-mediated neuronal inhibition in the hippocampus and associated cognitive impairment in rodents.[7][8] Similarly, it blocked the detrimental effects of the medium-chain fatty acid-producing gut bacteria Parabacteroides goldsteinii on memory in rodents.[7][8] In addition, fezagepras restored youthful memory function in aged rodents.[7][8]
References
[edit]- 1 2 "Liminal BioSciences". AdisInsight. 4 August 2022. Retrieved 6 July 2026.
- ↑ Li Y, Chung S, Li Z, Overstreet JM, Gagnon L, Grouix B, et al. (May 2018). "Fatty acid receptor modulator PBI-4050 inhibits kidney fibrosis and improves glycemic control". JCI Insight. 3 (10). doi:10.1172/jci.insight.120365. PMC 6012516. PMID 29769449.
- ↑ Khalil N, Manganas H, Ryerson CJ, Shapera S, Cantin AM, Hernandez P, et al. (March 2019). "Phase 2 clinical trial of PBI-4050 in patients with idiopathic pulmonary fibrosis". The European Respiratory Journal. 53 (3). doi:10.1183/13993003.00663-2018. PMC 6422836. PMID 30578394.
- ↑ Nguyen QT, Nsaibia MJ, Sirois MG, Calderone A, Tardif JC, Fen Shi Y, et al. (January 2020). "PBI-4050 reduces pulmonary hypertension, lung fibrosis, and right ventricular dysfunction in heart failure". Cardiovascular Research. 116 (1): 171–182. doi:10.1093/cvr/cvz034. PMID 30753422.
- ↑ Chen LH, Zhang Q, Xie X, Nan FJ (December 2020). "Modulation of the G-Protein-Coupled Receptor 84 (GPR84) by Agonists and Antagonists". Journal of Medicinal Chemistry. 63 (24): 15399–15409. doi:10.1021/acs.jmedchem.0c01378. PMID 33267584.
- ↑ Gagnon L, Leduc M, Thibodeau JF, Zhang MZ, Grouix B, Sarra-Bournet F, et al. (May 2018). "A Newly Discovered Antifibrotic Pathway Regulated by Two Fatty Acid Receptors: GPR40 and GPR84". The American Journal of Pathology. 188 (5): 1132–1148. doi:10.1016/j.ajpath.2018.01.009. PMID 29454750.
- 1 2 3 4 Cox TO, Devason AS, de Araujo A, Mason S, Subramanian M, Salvador AF, et al. (April 2026). "Intestinal interoceptive dysfunction drives age-associated cognitive decline". Nature. 652 (8109): 442–450. doi:10.1038/s41586-026-10191-6. PMC 13061634. PMID 41813891.
- 1 2 3 4 Hasavci D, Blank T (May 2026). "Rogue gut microbes derail memory". Immunity. 59 (5): 1177–1179. doi:10.1016/j.immuni.2026.04.008. PMID 42119367.
- ↑ "Stanford Scientists Reverse Age-Related Memory Loss by Targeting the Gut". SciTechDaily. 5 July 2026. Retrieved 13 July 2026.
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