Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Griffett K 

PROVIDER: S-EPMC9932051 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Griffett Kristine K   Burris Thomas P TP  

Frontiers in medicine 20230202


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 <i>de novo</i> 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 <i>de novo</i> l  ...[more]

Similar Datasets

| S-EPMC8583943 | biostudies-literature
| S-EPMC6538631 | biostudies-literature
| S-EPMC8042405 | biostudies-literature
2023-06-25 | GSE205980 | GEO
| S-EPMC8175718 | biostudies-literature
| S-EPMC4684448 | biostudies-literature
2024-11-27 | GSE276735 | GEO
| PRJNA848752 | ENA
| S-EPMC9061771 | biostudies-literature
| S-EPMC8792949 | biostudies-literature