A Novel Fc-FGF21 With Improved Resistance to Proteolysis, Increased Affinity Toward β-Klotho, and Enhanced Efficacy in Mice and Cynomolgus Monkeys

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 v...

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Veröffentlicht in:	Endocrinology (Philadelphia) 2017-05, Vol.158 (5), p.1314-1327
Hauptverfasser:	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
Format:	Artikel
Sprache:	eng
Schlagworte:	3T3-L1 Cells Affinity Animal models Animals Anti-Obesity Agents - chemical synthesis Anti-Obesity Agents - metabolism Anti-Obesity Agents - therapeutic use Binding C-Terminus Degradation Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Disease Models, Animal Drug Stability Energy metabolism Fc receptors Fibroblast growth factors Fibroblast Growth Factors - genetics Fibroblast Growth Factors - metabolism Fibroblast Growth Factors - therapeutic use Glucose metabolism Growth factors Half-Life HEK293 Cells Humans Immunogenicity Immunoglobulin Fc Fragments - genetics Immunoglobulin Fc Fragments - metabolism Immunoglobulin Fc Fragments - therapeutic use Klotho protein Lipid metabolism Lipids Macaca fascicularis Male Membrane Proteins - metabolism Metabolism Mice Mice, Inbred C57BL Monkeys Mutation Obesity - drug therapy Obesity - metabolism Pharmacodynamics Pharmacokinetics Plasma levels Protein Binding Protein Engineering - methods Proteolysis Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Recombinant Fusion Proteins - therapeutic use Treatment Outcome
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