Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases

Frontiers in Medicine

Medicine

Kristine Griffett¹  Thomas P. Burris² 

[1] Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, United States;The University of Florida Genetics Institute, Gainesville, FL, United States;

关键词: MAFLD;    NAFLD;    liver X receptors;    dyslipidemia;    hypercholesterolemia;    cirrhosis;    hepatocellular carcinoma;    pharmacology;   

DOI  :  10.3389/fmed.2023.1102469

 received in 2022-11-18, accepted in 2023-01-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

Activation of LXR activity by synthetic agonists has been the focus of many drug discovery efforts with a focus on treatment of dyslipidemia and atherosclerosis. Many agonists have been developed, but all have been hindered due to their ability to efficaciously stimulate de novo lipogenesis. Here, we review the development of LXR inverse agonists that were originally optimized for their ability to enable recruitment of corepressors leading to silencing of genes that drive de novo lipogenesis. Such compounds have efficacy in animal models of MAFLD, dyslipidemia, and cancer. Several classes of LXR inverse agonists have been identified and one is now in clinical trials for treatment of severe dyslipidemia.

【 授权许可】

Unknown   
Copyright © 2023 Griffett and Burris.