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Glucocorticoid receptors Library

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ChemDiv’s glucocorticoid receptors library contains 5,000 compounds.

Glucocorticoid receptor (GR), the founding member of the nuclear receptor superfamily, is a ubiquitously expressed, ligand-regulated vertebrate transcriptional regulatory factor (TRF). GR evolved to bind specific small lipophilic signaling molecules. This receptor is a protein shuttling between the cytoplasm and the nucleus upon binding to its ligand glucocorticoid, it modulates the transcription rates of glucocorticoid-responsive genes positively and negatively in the nucleus. Since it expressed in nearly all vertebrate cells GR directly up- and downregulates thousands of genes distinct to the cell type, it governs various aspects of development, metabolism, stress response, inflammation and other key tissue and organismal processes control of gene transcription is critical for development, physiology and homeostasis. Thus, aberrant transcription regulation commonly causes disease processes. [1]

Dysregulation in the negative feedback system of glucocorticoid hormone (for example cortisol) and its overexpression in humans can lead to many of the disease states. Diseases, that can be caused are Cushing’s syndrome, psychotic depression, diabetes, obesity, Alzheimer’s disease, neuropathic pain, drug abuse, and glaucoma. Selective modulators of the GR have been actively discovering in recent past years. One of the most well-known drugs is mifepristone which is a high- affinity antagonist of the glucocorticoid receptor. [2]

[1] E. R. Weikum, M. T. Knuesel, E. A. Ortlund, and K. R. Yamamoto, “Glucocorticoid receptor control of transcription: Precision and plasticity via allostery,” Nat. Rev. Mol. Cell Biol., vol. 18, no. 3, pp. 159–174, 2017, doi: 10.1038/nrm.2016.152.
[2] R. Clark, “Glucocorticoid Receptor Antagonists,” Curr. Top. Med. Chem., vol. 8, no. 9, pp. 813–838, 2008, doi: 10.2174/156802608784535011.
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