Glucocorticoids (GCs) are secreted from the adrenal gland in response to exposure to emotional and physiologic stressors and are responsible for modulating essential metabolic, cardiovascular, immune, and behavioral functions [1–3]. The glucocorticoid receptor (GR) belongs to a family of nuclear hormone receptors that are ligand-dependent transcription factors.
They are involved in activating and repressing gene expression, thereby changing the complement of proteins regulating key signaling pathways [4, 5].
Potential therapeutic applications of selective GR antagonists cover disease areas such as Cushing's syndrome, psychotic depression, diabetes, obesity, Alzheimer's disease, neuropathic pain, drug abuse, and glaucoma.
The Glucocorticoid Receptor Antagonist Library (1124 compounds in total) has been designed with receptor-based virtual screening using all available crystal structures of glucocorticoid receptor complexed with known antagonists (12 structures in total). The complexes have been superposed and divided into three groups by structural similarity. On the base of these groups, three different structural models were developed and then used to dock OTAVAchemicals Drug-like Green Collection. In the models, the following parameters have been taken into account: presence of two hydrophobic cores and minimum three hydrogen bonds with a number of key amino acid residues such as ARG:611, ASN:564, GLN:570, GLN:642, LEU:563, MET:604; THR:739. The models were validated with reference set of 1000 compounds obtained from ChEMBL database.
This library comprises drug-like compounds only.
All compounds are in stock, cherry-picking is available.
The library (DB, SD, XLS, PDF format) as well as the price-list is available on request. Feel free to contact us or use on-line form below to send an inquiry if you are interested to obtain this library or if you need more information.
Bamberger CM, Schulte HM, Chrousos GP. Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev 1996;17:245–61.
Pan D, Kocherginsky M, Conzen SD. Activation of the glucocorticoid receptor is associated with poor prognosis in estrogen receptor-negative breast cancer. Cancer Res 2011;71:6360–70.
Armaiz-Pena GN, Lutgendorf SK, Cole SW, Sood AK. Neuroendocrine modulation of cancer progression. Brain Behav Immun 2009;23:10–5.
McKenna NJ, O'Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 2002;108:465–74.
Lewis-Tuffin LJ, Cidlowski JA. The physiology of human glucocorticoid receptor beta (hGRbeta) and glucocorticoid resistance. Ann N Y Acad Sci 2006;1069:1–9.