Supporting data for "Development of the peptide antagonist targeting FGF23 for the treatment of hypophosphataemia"

FGF23 is an endocrine hormone that plays a critical role in phosphate and vitamin D metabolism. Its biological activity requires binding to the FGFR-α-Klotho receptor complex for signal transduction. Excessive FGF23 leads to hypophosphatemia and related disorders. Currently, there are limited FGF23-targeting drugs available on the market, and they have some side effects. Therefore, we designed FGF23-antagonizing peptides through virtual screening and introduced lipid modifications to enhance their plasma half-life. This peptide demonstrated FGF23-inhibitory activity in vitro and exhibited a 6.5-hour extension in plasma half-life in vivo. In vivo studies demonstrated its ability to counteract the physiological alterations induced by acute FGF23 injection. Finally, in hypophosphatemic mouse models, we found that both acute and short-term administration of this peptide elevated serum phosphate levels. Long-term administration of this peptide increased serum phosphate levels, enhanced bone formation, and restored both cardiac function and body weight.