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/).
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页数:12
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