Objective

Keratinocyte Growth Factor (KGF, also known as FGF7) is a member of the FGF family that binds to FGFR2b and promotes the proliferation and differentiation of epidermal cells and cells derived from the endoderm, such as alveolar epithelial cells, islet cells, and hepatocytes. It plays a key role in inducing the differentiation of pluripotent stem cells into islet-like cells, making it a vital factor in regenerative approaches for diabetes. However, like other FGFs such as FGF2, KGF suffers from poor stability at 37°C, rapidly losing activity and requiring frequent medium changes or high dose usage, posing significant operational and cost challenges. To overcome these challenges, we developed PG-012, a stable peptide-based alternative to KGF with equivalent biological activity.

Methods

Using PeptiDream’s Peptide Discovery Platform System (PDPS), we identified cyclic peptides that bind human FGFR2b. These were chemically linked to form dimeric structures designed to mimic KGF’s agonistic activity. Peptide sequences and linkers were optimized to generate the lead compound PG-012.

Results

PG-012 activated ERK signaling downstream of FGFR2b and promoted the proliferation of FGFR2b-overexpressing BaF3 cells. It also supported the differentiation of pluripotent stem cells into islet-like cells at levels comparable to KGF. Unlike recombinant KGF, PG-012 maintained full activity after prolonged incubation at 37°C, demonstrating superior thermal stability.

Conclusion

PG-012 is a promising KGF alternative with high stability and KGF-equivalent activity. It may reduce medium change frequency and reagent use, offering practical advantages for stem cell research and regenerative medicine.