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Liver receptor homolog-1: structures, related diseases, and drug discovery

Acta Pharmacologica Sinica (2024)Cite this article

Abstract

Liver receptor homolog-1 (LRH-1), a member of the nuclear receptor superfamily, is a ligand-regulated transcription factor that plays crucial roles in metabolism, development, and immunity. Despite being classified as an ‘orphan’ receptor due to the ongoing debate surrounding its endogenous ligands, recent researches have demonstrated that LRH-1 can be modulated by various synthetic ligands. This highlights the potential of LRH-1 as an attractive drug target for the treatment of inflammation, metabolic disorders, and cancer. In this review, we provide an overview of the structural basis, functional activities, associated diseases, and advancements in therapeutic ligand research targeting LRH-1.

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Fig. 1: Domain organization and structure features of the ligand binding domain (LBD) of human LRH-1 (hLRH-1).
Fig. 2: Regulation of LRH-1 transcriptional activity by co-regulators.
Fig. 3: Diseases and pathologies related to LRH-1.
Fig. 4: Co-crystal structures of small molecule modulators bound to hLRH-1 LBP.

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Acknowledgements

We gratefully acknowledge financial support from the National Key Research and Development Plan (grant 2022YFE0210600), the Joint Fund of Shandong Natural Science Foundation (grant ZR2022LSW026), the Science and Technology Program of Guangzhou, China (grant 202201010138).

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  1. These authors contributed equally: Tong Wu, Zhi-fang Lu

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  1. Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China

    Tong Wu, Zhi-fang Lu, Yang Liu & Yong Xu

  2. State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Center for Chemical Biology and Drug Discovery, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, China

    Tong Wu, Zhi-fang Lu, Hao-nan Yu, Xi-shan Wu & Yong Xu

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Wu, T., Lu, Zf., Yu, Hn. et al. Liver receptor homolog-1: structures, related diseases, and drug discovery. Acta Pharmacol Sin (2024). https://doi.org/10.1038/s41401-024-01276-x

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