Abstract
The NR superfamily comprises 48 transcription factors in humans that control a plethora of gene network programs involved in a wide range of physiologic processes. This review will summarize and discuss recent progress in NR biology and drug development derived from integrating various approaches, including biophysical techniques, structural studies, and translational investigation. We also highlight how defective NR signaling results in various diseases and disorders and how NRs can be targeted for therapeutic intervention via modulation via binding to synthetic lipophilic ligands. Furthermore, we also review recent studies that improved our understanding of NR structure and signaling.
Significance Statement Nuclear receptors (NRs) are ligand-regulated transcription factors that are critical regulators of myriad physiological processes. NRs serve as receptors for an array of drugs, and in this review, we provide an update on recent research into the roles of these drug targets.
Footnotes
- Received July 5, 2021.
- Revision received August 7, 2023.
- Accepted August 10, 2023.
This work was supported by research grants from National Institutes of Health [Grants AR069280, MH092769, MH093429, AG077160, and AG060769] (to T.P.B.), [Grants DK105845 and NS126204] (to K.G.), [Grant ES090057] (to J.A.C.), [Grant DK056123 and DK117940] (to A.N.H.), [Grant DK61935] (to M.T.), [Grant GM09614] (to P.W.), [Grant ES101586] (to A.M.J.), [Grant ES070065] (to K.S.K.), [Grants DK1033116, DK129646, and GM103546] (to T.S.H.), [Grants NS126204 and AG077160] (to B.E.), [Grants MH092779 and AR069280] (to J.K.W.), and the NIDDK Intramural Research Program (to D.F.), Saint Louis University (to I.M.S.d.V.) Department of Defense [Grants HT9425-23-1-0369 and HT9425-23-1-0389] (to K.L.B.) and [Grants W81XWH-16-1-0235 and W81XWH-19-1-0632] (to T.P.B.), the Florida Department of Health [Grant 9BC13] (to K.L.B.), the Department of Veterans Affairs [Grant BX005466] (to K.L.B), the Sylvester Comprehensive Cancer Center (to K.L.B.), the Cancer Prevention and Research Institute of Texas [Grant RP011444-P3] (to P.W.), and the American Heart Association [Grant 17SDG33670763] (to K.G.).
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- U.S. Government work not protected by U.S. copyright
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