PBI-4050 sodium salt

PBI-4050 acts as an agonist for GPR40 and as an antagonist or inverse agonist for GPR84.

Signaling Pathways >> GPCR/G Protein >> GPR40

Signaling Pathways >> GPCR/G Protein >> GPR84

Research Areas >> Inflammation/Immunology

GPR40, GPR84[1]

PBI-4050, a synthetic analogue of a medium–chain length fatty acid, binds to FFA receptor 1 (FFAR1/GPR40) and GPR84. To determine the potential role of PBI-4050 on diabetic kidney disease, The accelerated model of type 2 diabetic nephropathy, eNOS-/- db/db mice are utilized. Mice are treated with either vehicle or PBI-4050 (100 mg/kg) by daily gavage from 8-20 weeks of age. eNOS-/- db/db mice are moderately hypertensive, and PBI-4050 has no effect on blood pressure. Furthermore, compared with vehicle-treated mice, which exhibit a decrease in glomerular filtration rate (GFR) from 8-20 weeks, PBI-4050 preserves GFR. Podocyte number per glomerulus section markedly decreases from 8-20 weeks of age in vehicle-treated mice, while PBI-4050 treatment significantly slows this loss[1].

Mice[1] Type 2 diabetes eNOS-/- db/db mice on the BKS background are used. Genotyping is performed by PCR. A subset of eNOS-/- db/db male mice (8 weeks old) are randomized to 2 groups. One group is treated with PBI-4050 (100 mg/kg/day, n=10) , and the other group receive vehicle (water, n=12). Both PBI-4050 and water are given via daily gavage from 8-20 weeks. Mice are euthanized at 20 weeks of age. The second set of eNOS-/- db/db male mice are divided into 4 groups (8 mice in each group): vehicle (water), PBI-4050 (100 mg/kg/day), Captopril (0.75 mg/mL in drinking water), and PBI-4050 plus captopril. The treatment is begun at 16 weeks and ended at 24 weeks. The third set of eNOS-/- db/db male mice is divided into 2 groups (8 mice in each group): vehicle (water) and PBI-4050 (100 mg/kg/day). The treatment begins at 16 weeks and lasts up to 30 weeks or until death[1].

[1]. Li Y, et al. Fatty acid receptor modulator PBI-4050 inhibits kidney fibrosis and improves glycemic control. JCI Insight. 2018 May 17;3(10). pii: 120365.

TAK-875 | GW-1100 | GW9508 | 6-OAU | DC 260126 | GPR40 Activator 2 | GPR84 antagonist 8 | TUG-770 | AMG 837 | FAA1 agonist-1 | GPR40 Activator 1 | AM-1638 | GPR40 Agonist 2