Fezagepras

Fezagepras
Clinical data
Other names	Setogepram; PBI-4050; PBI4050
Drug class	FFAR1 (GPR40) agonist; GPR84 antagonist
Identifiers
	IUPAC name 2-(3-pentylphenyl)acetic acid;
CAS Number	1002101-19-0;
PubChem CID	24749700;
IUPHAR/BPS	10043;
DrugBank	DB15447;
ChemSpider	58107628;
UNII	879OVM0Y1S;
ChEMBL	ChEMBL4297635;
Chemical and physical data
Formula	C13H18O2
Molar mass	206.285 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCCCCC1=CC(=CC=C1)CC(=O)O;
	InChI InChI=1S/C13H18O2/c1-2-3-4-6-11-7-5-8-12(9-11)10-13(14)15/h5,7-9H,2-4,6,10H2,1H3,(H,14,15); Key:PEGQOIGYZLJMIB-UHFFFAOYSA-N;

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

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.

This drug article relating to the respiratory system is a stub. You can help Wikipedia by adding missing information.

[AdisInsight-1] 1 2 "Liminal BioSciences". AdisInsight. 4 August 2022. Retrieved 6 July 2026.

[2] 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.

[3] 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.

[4] 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.

[5] 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.

[6] 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.

[CoxDevasondeAraujo2026-7] 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.

[HasavciBlank2026-8] 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.

[SciTechDaily2026-9] "Stanford Scientists Reverse Age-Related Memory Loss by Targeting the Gut". SciTechDaily. 5 July 2026. Retrieved 13 July 2026.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

This page was redesigned at the edge.

References