Rationale-Based Engineering of a Potent Long-Acting FGF21 Analog for the Treatment of Type 2 Diabetes

@inproceedings{Hecht2012RationaleBasedEO,
  title={Rationale-Based Engineering of a Potent Long-Acting FGF21 Analog for the Treatment of Type 2 Diabetes},
  author={Randy Hecht and Yue-Sheng Li and Jeonghoon Sun and Ed Belouski and Michael J Hall and Todd Hager and Junming Yie and Wei Wang and Dwight Winters and S. E. Smith and Christopher S Spahr and Lei-Ting Tony Tam and Zhongnan Shen and Shanaka Stanislaus and Narumol Chinookoswong and Yvonne Yen Lin Lau and Allen Sickmier and Mark Leo Michaels and Thomas Boone and Murielle M V{\'e}niant and Jing Xu},
  booktitle={PloS one},
  year={2012}
}
Fibroblast growth factor 21 (FGF21) is a promising drug candidate for the treatment of type 2 diabetes. However, the use of wild type native FGF21 is challenging due to several limitations. Among these are its short half-life, its susceptibility to in vivo proteolytic degradation and its propensity to in vitro aggregation. We here describe a rationale-based protein engineering approach to generate a potent long-acting FGF21 analog with improved resistance to proteolysis and aggregation. A… CONTINUE READING

Citations

Publications citing this paper.
Showing 1-10 of 45 extracted citations

Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21.

The Journal of biological chemistry • 2016
View 6 Excerpts
Highly Influenced

Fibroblast Growth Factor 21 Analogs for Treating Metabolic Disorders

Front. Endocrinol. • 2015
View 5 Excerpts
Highly Influenced

Assessment of the metabolism of therapeutic proteins and antibodies.

Expert opinion on drug metabolism & toxicology • 2014
View 6 Excerpts
Highly Influenced

FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases.

Hormone molecular biology and clinical investigation • 2017
View 5 Excerpts
Highly Influenced

References

Publications referenced by this paper.
Showing 1-10 of 27 references

Kharitonenkov A (2011) Hormone-like fibroblast growth factors and metabolic regulation

YC Long
Biochim Biophys Acta • 2011
View 8 Excerpts
Highly Influenced

Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway.

Proceedings of the National Academy of Sciences of the United States of America • 2010
View 8 Excerpts
Highly Influenced

Different roles of N- and C- termini in the functional activity of FGF21.

Journal of cellular physiology • 2009
View 7 Excerpts
Highly Influenced

Similar Papers

Loading similar papers…