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Nuclear Receptors

Browse Nuclear Receptors

Browse Nuclear Receptors

Small molecule activators of nuclear receptors play a key role in modulating gene expression by enhancing the activity of ligand-dependent transcription factors. Nuclear receptors regulate diverse physiological processes, including lipid and glucose metabolism, inflammation, circadian rhythms, and cellular differentiation, by binding to specific DNA response elements and recruiting transcriptional machinery to control gene expression.

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Bexarotene, Free Acid

Bexarotene, Free Acid

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5-(4-(2-(Methyl(pyridin-2-yl)amino)ethoxy)benzyl)thiazolidine-2,4-dione

5-(4-(2-(Methyl(pyridin-2-yl)amino)ethoxy)benzyl)thiazolidine-2,4-dione

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PIOGLITAZONE

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2-Ethyl-6-methylpyridin-3-ol succinate

2-Ethyl-6-methylpyridin-3-ol succinate

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Agonists that bind the ligand-binding domain (LBD) directly initiate transcriptional activation, while allosteric modulators fine-tune receptor activity by modifying ligand binding kinetics or altering receptor interactions with coactivators and corepressors. Some nuclear receptors, such as the oestrogen receptor (ER) and glucocorticoid receptor (GR), function through both classical genomic pathways and rapid non-genomic signalling, expanding small molecule activator mechanisms.

Oestrogen-Related Receptors (ERRs) regulate mitochondrial biogenesis and energy metabolism. Agonists like XCT790 have been studied for potential applications in metabolic and neurodegenerative diseases. Glucocorticoid Receptors (GRs) agonists, including dexamethasone and prednisolone, exert potent anti-inflammatory and immunosuppressive effects, widely used in autoimmune diseases and asthma management.

As another example, agonists of the Vitamin D Receptor (VDR), which regulates calcium and phosphate homeostasis, immune function and cell proliferation. Calcitriol and synthetic analogues (e.g., paricalcitol) are used to manage chronic kidney disease and osteoporosis by modulating calcium metabolism. Small molecule nuclear receptor activators remain at the forefront of precision medicine, offering targeted approaches to modulating gene expression and cellular function.