MUTATED FIBROBLAST GROWTH FACTOR (FGF) 1 AND METHODS OF USE

摘要

The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a β-Klotho-binding protein, an FGFRlc-binding protein, a β-Klotho-binding protein and a FGFRlc- binding protein, a C-terminal region from FGF 19 or FGF21. In some examples, mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.