Cited by 122Fibroblast Growth Factor ResearchMonoclonal and Polyclonal Antibodies ResearchDiabetes Treatment and Management

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Development of a Novel Long-Acting Antidiabetic FGF21 Mimetic by Targeted Conjugation to a Scaffold Antibody

Huang, Jie, Ishino, Tetsuya, Chen, Gang, Rolzin, Paul, Osothprarop, Trina F., Retting, Kelsey, Li, Lingna, Jin, Ping, Matin, Marla J., Huyghe, Bernard, Talukdar, Saswata, Bradshaw, Curt W., Palanki, Moorthy, Violand, Bernard N., Woodnutt, Gary, Lappe, Rodney W., Ogilvie, Kathleen, Levin, Nancy·2013·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1124/jpet.113.204420

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Abstract

Fibroblast growth factor (FGF)21 improves insulin sensitivity, reduces body weight, and reverses hepatic steatosis in preclinical species. We generated long-acting FGF21 mimetics by site-specific conjugation of the protein to a scaffold antibody. Linking FGF21 through the C terminus decreased bioactivity, whereas bioactivity was maintained by linkage to selected internal positions. In mice, these CovX-Bodies retain efficacy while increasing half-life up to 70-fold compared with wild-type FGF21. A preferred midlinked CovX-Body, CVX-343, demonstrated enhanced in vivo stability in preclinical species, and a single injection improved glucose tolerance for 6 days in ob/ob mice. In diet-induced obese mice, weekly doses of CVX-343 reduced body weight, blood glucose, and lipids levels. In db/db mice, CVX-343 increased glucose tolerance, pancreatic β-cell mass, and proliferation. CVX-343, created by linkage of the CovX scaffold antibody to the engineered residue A129C of FGF21 protein, demonstrated superior preclinical pharmacodynamics by extending serum half-life of FGF21 while preserving full therapeutic functionality.

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Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504
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Badman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495
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Background
Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice
Xu, J., Lloyd, D. J., Hale, C., Stanislaus, S., Chen, M., Sivits, G., Vonderfecht, S., Hecht, R., Li, Y.-S., Lindberg, R. A., et al. (2009) · Diabetes · doi:10.2337/db08-0392 · Cited by 1,151
Fibroblast Growth Factor 21 Corrects Obesity in Mice
Coskun, T., Bina, H. A., Schneider, M. A., Dunbar, J. D., Hu, C. C., Chen, Y., Moller, D. E., & Kharitonenkov, A. (2008) · Endocrinology · doi:10.1210/en.2008-0816 · Cited by 1,031
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Kurosu, H., Choi, M., Ogawa, Y., Dickson, A. S., Goetz, R., Eliseenkova, A. V., Mohammadi, M., Rosenblatt, K. P., Kliewer, S. A., & Kuro-o, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704165200 · Cited by 748
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PEGylation of therapeutic proteins
Jevševar, S., Kunstelj, M., & Porekar, V. G. (2010) · Biotechnology Journal · doi:10.1002/biot.200900218 · Cited by 681

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Self-citation

Authors: Huang, J., Ishino, T., Chen, G., Rolzin, P., Osothprarop, T. F., Retting, K., Li, L., Jin, P., Matin, M. J., Huyghe, B., Talukdar, S., Bradshaw, C. W., Palanki, M., Violand, B. N., Woodnutt, G., Lappe, R. W., Ogilvie, K., & Levin, N.
Affiliations: Pfizer (United States) (US)
ORCID: Chen, Gang
Li, Lingna
Talukdar, Saswata
Venue: The Journal of Pharmacology and Experimental Therapeutics
Publisher: Elsevier BV
Published: 2013-08
Volume: 346
Issue: 2
Pages: 270-280
ISSN: 0022-3565 (ISSN-L)
DOI: 10.1124/jpet.113.204420
OpenAlex: W2029880965
Cited by: 121
References: 36
Citations by year: 2026: 4 · 2025: 9 · 2024: 8 · 2023: 5 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 7 · 2018: 9 · 2017: 11 · 2016: 9 · 2015: 19 · 2014: 9 · 2013: 3
FWCI: 5.97
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: FGF21, protein conjugation, long-acting drugs, protein half-life extension, insulin sensitivity, glucose tolerance, obesity, type 2 diabetes, ob/ob mice, db/db mice, hepatic steatosis
MeSH terms: Animals, Antibodies, Body Weight, Cysteine, Delayed-Action Preparations, Diabetes Mellitus, Energy Metabolism, Fibroblast Growth Factors, Humans, Hypoglycemic Agents, Immunoglobulin Fab Fragments, Lysine, Macaca fascicularis, Male, Mice, Obese, Recombinant Proteins, Rats, Sprague-Dawley, Molecular Mimicry, 3T3-L1 Cells, Insulin-Secreting Cells, Mice, Rats

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Development of a Novel Long-Acting Antidiabetic FGF21 Mimetic by Targeted Conjugation to a Scaffold Antibody

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