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Synonyms: fibroblast growth factor 23
Compound class: Endogenous peptide in human, mouse or rat
Comment: FGF-23 regulates phosphate homeostasis and calcium transport in the kidney . The full-length 327 amino acid protein is functional, and is deactivated by proteolytic cleavage which generates N-terminal and C-terminal chains. Mutation of the cleavage site causes autosomal dominant hypophosphatemic rickets (ADHR), and other gene alterations are associated with hyperphosphatemic familial tumoral calcinosis (HFTC). Antibody-driven inactivation of FGF-23 is being investigated as a pharmacological intervention in these indications. Burosumab (KRN23) is one such FGF-23 neutralising antibody in clinical development.
A FGFR1 isoform [FGFR1(IIIc)] in complex with the Klotho protein (KL; Q9UEF7) forms a high affinity receptor for FGF-23 [1-2,4].
1. Chen G, Liu Y, Goetz R, Fu L, Jayaraman S, Hu MC, Moe OW, Liang G, Li X, Mohammadi M. (2018)
α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling.
Nature, 553 (7689): 461-466. [PMID:29342138]
2. Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW et al.. (2006)
Regulation of fibroblast growth factor-23 signaling by klotho.
J Biol Chem, 281 (10): 6120-3. [PMID:16436388]
3. Tsagalis G, Psimenou E, Manios E, Laggouranis A. (2009)
Fibroblast growth factor 23 (FGF23) and the kidney.
Int J Artif Organs, 32 (4): 232-9. [PMID:19569031]
4. Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T. (2006)
Klotho converts canonical FGF receptor into a specific receptor for FGF23.
Nature, 444 (7120): 770-4. [PMID:17086194]
5. Yamazaki Y, Urakawa I, Yoshida H, Aono Y, Yamashita T, Shimada T, Hasegawa H. (2011)
Anti FGF23 antibody and a pharmaceutical composition comprising the same.
Patent number: US7883705. Assignee: Kyowa Hakko Kirin Co., Ltd.. Priority date: 15/02/2007. Publication date: 08/02/2011.