Article
A Novel Fc-FGF21 With Improved Resistance to Proteolysis, Increased Affinity Toward β-Klotho, and Enhanced Efficacy in Mice and Cynomolgus Monkeys.
Endocrinology - 1 May 2017
Stanislaus Shanaka, Hecht Randy, Yie Junming, Hager Todd, Hall Michael, Spahr Chris, Wang Wei, Weiszmann Jennifer, Li Yang, Deng Liying, Winters Dwight, Smith Stephen, Zhou Lei, Li Yuesheng, Véniant Murielle M, Xu Jing
Abstract excerpt
Fibroblast growth factor (FGF) 21 is a natural hormone that modulates glucose, lipid, and energy metabolism. Previously, we engineered an Fc fusion FGF21 variant with two mutations, Fc-FGF21(RG), to extend the half-life and reduce aggregation and in vivo degradation of FGF21. We now describe a new variant developed to reduce the extreme C-terminal degradation and improve the binding affinity to β-Klotho. We...
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