FGF19 and FGF21: In NASH we trust

被引:58
|
作者
Talukdar, Saswata [1 ]
Kharitonenkov, Alexei [2 ]
机构
[1] Merck & Co Inc, 213 East Grand Ave, San Francisco, CA 94080 USA
[2] AK Biotechnol LLC, 3812 Verdure Lane, Zionsville, IN 46077 USA
来源
MOLECULAR METABOLISM | 2020年 / 46卷
关键词
FGF21; FGF19; NASH; Metabolism; Drug development; Clinical trials; FIBROBLAST-GROWTH-FACTOR; LONG-ACTING FGF21; INCREASES ENERGY-EXPENDITURE; DECREASES BODY-WEIGHT; FACTOR; 21; ANALOG; BETA-KLOTHO; INSULIN SENSITIVITY; CIRCULATING FGF21; PPAR-ALPHA; REGULATES METABOLISM;
D O I
10.1016/j.molmet.2020.101152
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: FGF19 and FGF21 have shown therapeutic promise since their discovery, attested by the fact there are at least 5 assets that activate the FGFR/KLB pathway and one FGF19 analog in clinical development. Methods: We performed a detailed analyses of published preclinical and clinical data to offer insights into the mechanism of action, as well as PK/PD and efficacy data of the clinical assets. Results: Scouring the literature, we offer mechanistic insights from preclinical data using rodents and non-human primates and pharmacodynamic data from clinical studies. Conclusion: The basic and applied science around endocrine FGFs has evolved exponentially over the years with FGF19 and FGF21 analogs are now entering Phase 3 clinical research. (c) 2020 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
引用
收藏
页数:12
相关论文
共 50 条
  • [1] FGF19 subfamily members: FGF19 and FGF21
    Katarzyna Dolegowska
    Malgorzata Marchelek-Mysliwiec
    Monika Nowosiad-Magda
    Michal Slawinski
    Barbara Dolegowska
    Journal of Physiology and Biochemistry, 2019, 75 : 229 - 240
  • [2] FGF19 subfamily members: FGF19 and FGF21
    Dolegowska, Katarzyna
    Marchelek-Mysliwiec, Malgorzata
    Nowosiad-Magda, Monika
    Slawinski, Michal
    Dolegowska, Barbara
    JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY, 2019, 75 (02) : 229 - 240
  • [3] FGF19 and FGF21 for the Treatment of NASH-Two Sides of the Same Coin? Differential and Overlapping Effects of FGF19 and FGF21 From Mice to Human
    Henriksson, Emma
    Andersen, Birgitte
    FRONTIERS IN ENDOCRINOLOGY, 2020, 11
  • [4] Pharmacological actions of FGF19 and FGF21 revealed
    Morris, Alan
    NATURE REVIEWS ENDOCRINOLOGY, 2017, 13 (12) : 690 - 690
  • [5] Pharmacological actions of FGF19 and FGF21 revealed
    Alan Morris
    Nature Reviews Endocrinology, 2017, 13 : 690 - 690
  • [6] Fundamentals of FGF19 & FGF21 Action In Vitro and In Vivo
    Adams, Andrew C.
    Coskun, Tamer
    Rovira, Armando R. Irizarry
    Schneider, Michael A.
    Raches, David W.
    Micanovic, Radmila
    Bina, Holly A.
    Dunbar, James D.
    Kharitonenkov, Alexei
    PLOS ONE, 2012, 7 (05):
  • [7] Selective Regulation of FGF19 and FGF21 Expression by Cellular and Nutritional Stress
    Shimizu, Makoto
    Morimoto, Hitomi
    Maruyama, Ryuto
    Inoue, Jun
    Sato, Ryuichiro
    JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY, 2015, 61 (02) : 154 - 160
  • [8] Alteration in serum concentrations of FGF19, FGF21, and FGF23 in patients with urothelial carcinoma
    Li, Jian-Ri
    Chiu, Kun-Yuan
    Ou, Yen-Chuan
    Wang, Shian-Shiang
    Chen, Chuan-Su
    Yang, Cheng-Kuang
    Ho, Hao-Chung
    Cheng, Chen-Li
    Yang, Chi-Rei
    Chen, Cheng-Che
    Wang, Shu-Chi
    Lin, Chia-Yen
    Hung, Sheng-Chun
    Hsu, Chiann-Yi
    Chen, Chun-Jung
    BIOFACTORS, 2019, 45 (01) : 62 - 68
  • [9] Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23
    Degirolamo, Chiara
    Sabba, Carlo
    Moschetta, Antonio
    NATURE REVIEWS DRUG DISCOVERY, 2016, 15 (01) : 51 - 69
  • [10] Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23
    Chiara Degirolamo
    Carlo Sabbà
    Antonio Moschetta
    Nature Reviews Drug Discovery, 2016, 15 : 51 - 69