INHIBITING BINDING OF FGF23 TO THE BINARY FGFR-KLOTHO COMPLEX FOR THE TREATMENT OF HYPOPHOSPHATEMIA

摘要

The present invention is directed to a method of treating hypophosphatemia in a subject. This method involves selecting a subject with hypophosphatemia associated with elevated or normal FGF23 and administering to the selected subject an inhibitor of FGF23-Klotho-FGF receptor complex formation under conditions effective to treat the hypophosphatemia. The present invention is also directed to a method of screening for compounds suitable for treatment of hypophosphatemia associated with elevated or normal FGF23. This method involves providing FGF23, FGFR-Klotho complex, and one or more candidate compounds. The FGF23, the FGFR-Klotho complex, and the candidate compounds are combined under conditions effective for the FGF23 and the binary FGFR-Klotho complex to form a ternary complex if present by themselves. This method also involves identifying the candidate compounds, which prevent formation of the complex as being potentially suitable in treating hypophosphatemic conditions associated with elevated or normal FGF23. A method of screening the specificity of compounds which prevent formation of the FGF23-Klotho-FGFR complex is also disclosed.