FGF21 Can Be Mimicked In Vitro and In Vivo by a Novel Anti-FGFR1c/β-Klotho Bispecific Protein

PLoS ONE

Volumn 8, Issue 4, 2013, Pages

  Smith, Richard ^a   Duguay, Amy ^a   Bakker, Alice ^a   Li, Peng ^a   Weiszmann, Jennifer ^a   Thomas, Melissa R ^a   Alba, Benjamin M ^a   Wu, Xinle ^a   Gupte, Jamila ^a   Yang, Li ^a   Stevens, Jennitte ^a   Hamburger, Agnes ^a   Smith, Stephen ^a   Chen, Jiyun ^a   Komorowski, Renee ^a   Moore, Kevin W ^a   Véniant, Murielle M ^a   Li, Yang ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS AFFECTING METABOLISM; ANTIOBESITY AGENT; BETA KLOTHO PROTEIN; C2240 PEPTIDE; C2987 PEPTIDE; C3201 PEPTIDE; C3201 PEPTIDE HUMAN SERUM ALBUMIN FUSION PROTEIN; C3209 PEPTIDE; EPITOPE; FC FIBROBLAST GROWTH FACTOR 21 FUSION PROTEIN; FIBROBLAST GROWTH FACTOR 21; FIBROBLAST GROWTH FACTOR RECEPTOR; FIBROBLAST GROWTH FACTOR RECEPTOR 1C; HYBRID PROTEIN; KLOTHO PROTEIN; MOLECULAR SCAFFOLD; POLYPEPTIDE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG DETERMINATION; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFECT; DRUG HALF LIFE; DRUG MECHANISM; DRUG MEGADOSE; DRUG RECEPTOR BINDING; FEMALE; HAPLORHINI; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LOW DRUG DOSE; MALE; MOUSE; NONHUMAN; PHAGE DISPLAY; PLASMA HALF LIFE; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; SINGLE DRUG DOSE; WEIGHT REDUCTION;

AMINO ACID SEQUENCE; ANIMALS; ANTI-OBESITY AGENTS; BINDING SITES; BINDING, COMPETITIVE; BODY WEIGHT; CELL LINE; DRUG EVALUATION, PRECLINICAL; FIBROBLAST GROWTH FACTORS; INSULIN; MACACA FASCICULARIS; MALE; MEMBRANE PROTEINS; MICE; MOLECULAR MIMICRY; MOLECULAR SEQUENCE DATA; OBESITY; PEPTIDES; PROTEIN BINDING; RATS; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 1; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 4; RECOMBINANT FUSION PROTEINS; SERUM ALBUMIN; SIGNAL TRANSDUCTION; TRIGLYCERIDES;

ANIMALIA; MACACA FASCICULARIS;

EID: 84876452595     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0061432     Document Type: Article

References (45)

1. Fukumoto S, (2008) Actions and mode of actions of FGF19 subfamily members. Endocr J 55: 23-31.
2. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, et al. (2005) FGF-21 as a novel metabolic regulator. J Clin Invest 115: 1627-1635.
3. Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, et al. (2007) Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell Metab 5: 415-425.
4. Badman MK, Koester A, Flier JS, Kharitonenkov A, Maratos-Flier E, (2009) Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis. Endocrinology 150: 4931-4940.
5. Kharitonenkov A, Wroblewski VJ, Koester A, Chen YF, Clutinger CK, et al. (2007) The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology 148: 774-781.
6. Xu J, Lloyd DJ, Hale C, Stanislaus S, Chen M, et al. (2009) Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 58: 250-259.
7. Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, et al. (2008) Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149: 6018-6027.
8. Mai K, Schwarz F, Bobbert T, Andres J, Assmann A, et al. (2011) Relation between fibroblast growth factor-21, adiposity, metabolism, and weight reduction. Metabolism 60: 306-311.
9. Veniant MM, Komorowski R, Chen P, Stanislaus S, Winters K, et al. (2012) Long-Acting FGF21 Has Enhanced Efficacy in Diet-Induced Obese Mice and in Obese Rhesus Monkeys. Endocrinology 153: 4192-4203.
10. Dostalova I, Haluzikova D, Haluzik M, (2009) Fibroblast growth factor 21: a novel metabolic regulator with potential therapeutic properties in obesity/type 2 diabetes mellitus. Physiol Res 58: 1-7.
11. Kharitonenkov A, Shanafelt AB, (2009) FGF21: a novel prospect for the treatment of metabolic diseases. Curr Opin Investig Drugs 10: 359-364.
12. Kharitonenkov A, Shanafelt AB, (2008) Fibroblast growth factor-21 as a therapeutic agent for metabolic diseases. BioDrugs 22: 37-44.
13. Veniant MM, Komorowski R, Chen P, Stanislaus S, Winters K, et al. (2012) Long-Acting FGF21 Has Enhanced Efficacy in Diet-Induced Obese Mice and in Obese Rhesus Monkeys. Endocrinology 153 (9) (): 4192-4203.
14. Ogawa Y, Kurosu H, Yamamoto M, Nandi A, Rosenblatt KP, et al. (2007) BetaKlotho is required for metabolic activity of fibroblast growth factor 21. Proc Natl Acad Sci U S A 104: 7432-7437.
15. Fon Tacer K, Bookout AL, Ding X, Kurosu H, John GB, et al. (2010) Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol 24: 2050-2064.
16. Ge H, Baribault H, Vonderfecht S, Lemon B, Weiszmann J, et al. (2012) Characterization of a FGF19 variant with altered receptor specificity revealed a central role for FGFR1c in the regulation of glucose metabolism. PLoS One 7: e33603.
17. Foltz IN, Hu S, King C, Wu X, Yang C, et al. (2012) Treating Diabetes and Obesity with an FGF21-Mimetic Antibody Activating the betaKlotho/FGFR1c Receptor Complex. Sci Transl Med 4: 162ra153.
18. Ding X, Boney-Montoya J, Owen BM, Bookout AL, Coate KC, et al. (2012) betaKlotho is required for fibroblast growth factor 21 effects on growth and metabolism. Cell Metab 16: 387-393.
19. Adams AC, Cheng CC, Coskun T, Kharitonenkov A, (2012) FGF21 Requires betaklotho to Act In Vivo. PLoS One 7: e49977.
20. Harmer NJ, Ilag LL, Mulloy B, Pellegrini L, Robinson CV, et al. (2004) Towards a resolution of the stoichiometry of the fibroblast growth factor (FGF)-FGF receptor-heparin complex. J Mol Biol 339: 821-834.
21. Yie J, Wang W, Deng L, Tam LT, Stevens J, et al. (2012) Understanding the physical interactions in the FGF21/FGFR/beta-Klotho complex: structural requirements and implications in FGF21 signaling. Chem Biol Drug Des 79: 398-410.
22. Gupte J, Yang L, Wu X, Weiszmann J, Hecht R, et al. (2011) The FGFR D3 Domain Determines Receptor Selectivity For Fibroblast Growth Factor 21. J Mol Biol 408 (3) (): 491-502.
23. Silverman J, Liu Q, Bakker A, To W, Duguay A, et al. (2005) Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains. Nat Biotechnol 23: 1556-1561.
24. Kurosu H, Choi M, Ogawa Y, Dickson AS, Goetz R, et al. (2007) Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem 282: 26687-26695.
25. Wu X, Ge H, Lemon B, Vonderfecht S, Weiszmann J, et al. (2010) FGF19-induced hepatocyte proliferation is mediated through FGFR4 activation. J Biol Chem 285: 5165-5170.
26. Wu X, Ge H, Lemon B, Weiszmann J, Gupte J, et al. (2009) Selective activation of FGFR4 by an FGF19 variant does not improve glucose metabolism in ob/ob mice. Proc Natl Acad Sci U S A 106: 14379-14384.
27. Xie MH, Holcomb I, Deuel B, Dowd P, Huang A, et al. (1999) FGF-19, a novel fibroblast growth factor with unique specificity for FGFR4. Cytokine 11: 729-735.
28. Plotnikov AN, Hubbard SR, Schlessinger J, Mohammadi M, (2000) Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Cell 101: 413-424.
29. Gao Z, Bai G, Chen J, Zhang Q, Pan P, et al. (2009) Development, characterization, and evaluation of a fusion protein of a novel glucagon-like peptide-1 (GLP-1) analog and human serum albumin in Pichia pastoris. Biosci Biotechnol Biochem 73: 688-694.
30. Muller D, Karle A, Meissburger B, Hofig I, Stork R, et al. (2007) Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. J Biol Chem 282: 12650-12660.
31. Muller N, Schneider B, Pfizenmaier K, Wajant H, (2010) Superior serum half life of albumin tagged TNF ligands. Biochem Biophys Res Commun 396: 793-799.
32. Sung C, Nardelli B, LaFleur DW, Blatter E, Corcoran M, et al. (2003) An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates. J Interferon Cytokine Res 23: 25-36.
33. Huang Z, Wang H, Lu M, Sun C, Wu X, et al. (2011) A Better Anti-Diabetic Recombinant Human Fibroblast Growth Factor 21 (rhFGF21) Modified with Polyethylene Glycol. PLoS One 6: e20669.
34. Kontermann RE, (2009) Strategies to extend plasma half-lives of recombinant antibodies. BioDrugs 23: 93-109.
35. Mu J, Pinkstaff J, Li Z, Skidmore L, Li N, et al. (2012) FGF21 analogs of sustained action enabled by orthogonal biosynthesis demonstrate enhanced antidiabetic pharmacology in rodents. Diabetes 61: 505-512.
36. Bendele A, Seely J, Richey C, Sennello G, Shopp G, (1998) Short communication: renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins. Toxicol Sci 42: 152-157.
37. Dingermann T, (2008) Recombinant therapeutic proteins: production platforms and challenges. Biotechnol J 3: 90-97.
38. Yie J, Hecht R, Patel J, Stevens J, Wang W, et al. (2009) FGF21 N- and C-termini play different roles in receptor interaction and activation. FEBS Lett 583: 19-24.
39. Micanovic R, Raches DW, Dunbar JD, Driver DA, Bina HA, et al. (2009) Different roles of N- and C- termini in the functional activity of FGF21. J Cell Physiol 219: 227-234.
40. Wu AL, Kolumam GA, Stawicki S, Chen Y, Li J, et al. (2011) Amelioration of type 2 diabetes by antibody-mediated activation of fibroblast growth factor receptor 1. Sci Transl Med 3: 113ra126.
41. Berglund ED, Li CY, Bina HA, Lynes SE, Michael MD, et al. (2009) Fibroblast growth factor 21 controls glycemia via regulation of hepatic glucose flux and insulin sensitivity. Endocrinology 150: 4084-4093.
42. Cuevas-Ramos D, Almeda-Valdes P, Aguilar-Salinas CA, Cuevas-Ramos G, Cuevas-Sosa AA, et al. (2009) The role of fibroblast growth factor 21 (FGF21) on energy balance, glucose and lipid metabolism. Curr Diabetes Rev 5: 216-220.
43. Xu J, Stanislaus S, Chinookoswong N, Lau YY, Hager T, et al. (2009) Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin resistant mouse models-Association with liver and adipose tissue effects. Am J Physiol Endocrinol Metab 297 (5) (): E1105-1114.
44. Bussiere JL, (2003) Animal models as indicators of immunogenicity of therapeutic proteins in humans. Dev Biol (Basel) 112: 135-139.
45. National Research Council (2011) Guide for the care and use of laboratory animals. Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research. Washington, DC: National Academies Press. xxv, 220 p.