Table 3. Selected List of FGF21 Mimetics with Reported Lipid-Lowering Properties.
| Name | Company | Structural feature/Modification | Lipid-lowering effect | Reference |
|---|---|---|---|---|
| R1MAb | Genentech | β-Klotho-independent agonistic mAb against FGFR1b/c | ↓ Hepatic TC & TG; ↓ serum TC & NEFA (db/db mice) |
[43] |
| Fc-FGF21(RG) | Amgen | L98R (↓ aggregation); P171G (↓ proteolysis); Fusion to Fc (↑ half-life) |
↓ Serum TC & TG (DIO mice) ↓ Fasted serum TG (DIO monkeys) |
[45] |
| LY2405319 | Lilly | L118C, A134C (disulphide bridge); S167A (↓ glycosylation in yeast); HPIP deletion (↓ proteolysis) |
↓ Serum TG, TC & VLDL-C; ↑ serum HDL-C (diabetic rhesus monkeys) ↓ Serum TG, TC, LDL-C & VLDL-C; ↑ serum HDL-C (humans) |
[48,51] |
| PF-05231023 | Pfizer | A129C (linkage to CVX-200); CVX-200 conjugation (↑ half-life) |
↓ Serum TG & VLDL-C; ↑ serum HDL-C (obese cynomolgus monkeys) ↓ Serum TG, TC & LDL-C; ↑ serum HDL-C (humans) |
[53] |
FGF21, fibroblast growth factor 21; R1MAb, FGFR1 with monoclonal anti-FGFR1 antibody; mAb, monoclonal antibody; FGFR1, FGF receptor 1; TC, total cholesterol; TG, triglyceride; NEFA, non-esterified fatty acid; Fc, antibody constant domain; DIO, diet-induced obesity; HPIP, histidine-prolineisoleucine- proline; VLDL-C, very low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; CVX, CovX-body.