ArticleScientific reports2018
Glyco-engineered Long Acting FGF21 Variant with Optimal Pharmaceutical and Pharmacokinetic Properties to Enable Weekly to Twice Monthly Subcutaneous Dosing.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Unraveling the role of FGF21 in epilepsy disease: mechanistic insights and therapeutic Potential.Metabolic brain disease · 2026Review
- Review
- GDF15 Analogues Acting as GFRAL Ligands.ChemMedChem · 2025Review
- A Novel GLP-1 and FGF21 Fusion Protein for the Treatment of Non-alcoholic Steatohepatitis (NASH).Advanced pharmaceutical bulletin · 2025Article
- A Novel Recombinant Human FGF21 Analog with High Glycosylation Has a Prolonged Half-Life and Affects Glycemic and Body Weight Control.International journal of molecular sciences · 2025Article
- Treating metabolic dysfunction-associated steatohepatitis: The fat-trimming FGF21 approach.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Pathology and Therapeutic Significance of Fibroblast Growth Factors.Targets (Basel) · 2025Article
- Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.Neurochemical research · 2025Review
- Computer-aided engineering of stabilized fibroblast growth factor 21.Computational and structural biotechnology journal · 2024Article
- Novel treatment for PXE: Recombinant ENPP1 enzyme therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Analysis of Functional Promoter of Camel FGF21 Gene and Identification of Small Compounds Targeting FGF21 Protein.Veterinary sciences · 2023Article
- Article
- Fc-GDF15 glyco-engineering and receptor binding affinity optimization for body weight regulation.Scientific reports · 2021Article
- FGF19 and FGF21: In NASH we trust.Molecular metabolism · 2021Review
- Dynamic folding modulation generates FGF21 variant against diabetes.EMBO reports · 2021Article
- Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine.Frontiers in endocrinology · 2021Review
- Improving the Pharmacodynamics and In Vivo Activity of ENPP1-Fc Through Protein and Glycosylation Engineering.Clinical and translational science · 2021Article
- Characterization and Quantification of an Fc-FGF21 Fusion Protein in Rat Serum Using Immunoaffinity LC-MS.The AAPS journal · 2019Article
- Fibroblast growth factors in control of lipid metabolism: from biological function to clinical application.Current opinion in lipidology · 2019Review
- Intestinal serine protease inhibition increases FGF21 and improves metabolism in obese mice.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
Corrections and comments
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Authors and funding
26 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacological administration of FGF21 analogues has shown robust body weight reduction and lipid profile improvement in both dysmetabolic animal models and metabolic disease patients. Here we report the design, optimization, and characterization of a long acting glyco-variant of FGF21. Using a combination of N-glycan engineering for enhanced protease resistance and improved solubility, Fc fusion for further half-life extension, and a single point mutation for improving manufacturability in Chinese Hamster Ovary cells, we created a novel FGF21 analogue, Fc-FGF21[R19V][N171] or PF-06645849, with substantially improved solubility and stability profile that is compatible with subcutaneous (SC) administration. In particular, it showed a low systemic clearance (0.243 mL/hr/kg) and long terminal half-life (~200 hours for intact protein) in cynomolgus monkeys that approaches those of monoclonal antibodies. Furthermore, the superior PK properties translated into robust improvement in glucose tolerance and the effects lasted 14 days post single SC dose in ob/ob mice. PF-06645849 also caused greater body weight loss in DIO mice at lower and less frequent SC doses, compared to previous FGF21 analogue PF-05231023. In summary, the overall PK/PD and pharmaceutical profile of PF-06645849 offers great potential for development as weekly to twice-monthly SC administered therapeutic for chronic treatment of metabolic diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.