Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases
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, w...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1102469/full |
| _version_ | 1828046212685627392 |
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| author | Kristine Griffett Thomas P. Burris |
| author_facet | Kristine Griffett Thomas P. Burris |
| author_sort | Kristine Griffett |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T18:23:49Z |
| format | Article |
| id | doaj.art-c72500ab581f4ceda761ea45ab25efff |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-10T18:23:49Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-c72500ab581f4ceda761ea45ab25efff2023-02-02T06:53:23ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-02-011010.3389/fmed.2023.11024691102469Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseasesKristine Griffett0Thomas P. Burris1Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesThe University of Florida Genetics Institute, Gainesville, FL, United StatesActivation 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.https://www.frontiersin.org/articles/10.3389/fmed.2023.1102469/fullMAFLDNAFLDliver X receptorsdyslipidemiahypercholesterolemiacirrhosis |
| spellingShingle | Kristine Griffett Thomas P. Burris Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases Frontiers in Medicine MAFLD NAFLD liver X receptors dyslipidemia hypercholesterolemia cirrhosis |
| title | Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases |
| title_full | Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases |
| title_fullStr | Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases |
| title_full_unstemmed | Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases |
| title_short | Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases |
| title_sort | development of lxr inverse agonists to treat mafld nash and other metabolic diseases |
| topic | MAFLD NAFLD liver X receptors dyslipidemia hypercholesterolemia cirrhosis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1102469/full |
| work_keys_str_mv | AT kristinegriffett developmentoflxrinverseagoniststotreatmafldnashandothermetabolicdiseases AT thomaspburris developmentoflxrinverseagoniststotreatmafldnashandothermetabolicdiseases |