INHIBITING BINDING OF FGF23 TO THE BINARY FGFR-KLOTHO COMPLEX FOR THE TREATMENT OF HYPOPHOSPHATEMIA
First Claim
1. A method of screening for compounds suitable for treatment of a hypophosphatemic condition, said method comprising:
- providing FGF23;
providing binary FGFR-Klotho complex;
providing one or more candidate compounds;
combining the FGF23, the binary FGFR-Klotho complex, and the candidate compounds under conditions effective for the FGF23 and the binary FGFR-Klotho complex to form a ternary complex if present by themselves; and
identifying the candidate compounds which prevent formation of the complex as being potentially suitable in treating hypophosphatemia associated with elevated or normal FGF23.
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Abstract
The present invention is directed to a method of treating hypophosphatemia in a subject. 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.
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Citations
15 Claims
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1. A method of screening for compounds suitable for treatment of a hypophosphatemic condition, said method comprising:
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providing FGF23; providing binary FGFR-Klotho complex; providing one or more candidate compounds; combining the FGF23, the binary FGFR-Klotho complex, and the candidate compounds under conditions effective for the FGF23 and the binary FGFR-Klotho complex to form a ternary complex if present by themselves; and identifying the candidate compounds which prevent formation of the complex as being potentially suitable in treating hypophosphatemia associated with elevated or normal FGF23. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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12. A method of screening the specificity of compounds which prevent formation of the FGF23-Klotho-FGFR complex, said method comprising:
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providing FGF19; providing binary FGFR-β
Klotho complex;providing one or more candidate compounds; combining the FGF19, the binary FGFR-β
Klotho complex, and the candidate compounds under conditions effective for the FGF19 and the binary FGFR-β
Klotho complex to form a ternary complex if present by themselves; andidentifying the candidate compounds which do not interfere with formation of the complex as being specific and potentially suitable in treating hypophosphatemia associated with elevated or normal FGF23 levels. - View Dependent Claims (13, 14, 15)
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Specification