@article{APS10673,
author = {Jin-ping Pang and Xue-ping Hu and Yun-xia Wang and Jia-ning Liao and Xin Chai and Xu-wen Wang and Chao Shen and Jia-jia Wang and Lu-lu Zhang and Xin-yue Wang and Feng Zhu and Qin-jie Weng and Lei Xu and Ting-jun Hou and Dan Li},
title = {Discovery of a novel nonsteroidal selective glucocorticoid receptor modulator by virtual screening and bioassays},
journal = {Acta Pharmacologica Sinica},
volume = {43},
number = {9},
year = {2022},
keywords = {},
abstract = {Synthetic glucocorticoids (GCs) have been widely used in the treatment of a broad range of inflammatory diseases, but their clinic use is limited by undesired side effects such as metabolic disorders, osteoporosis, skin and muscle atrophies, mood disorders and hypothalamic-pituitary-adrenal (HPA) axis suppression. Selective glucocorticoid receptor modulators (SGRMs) are expected to have promising anti-inflammatory efficacy but with fewer side effects caused by GCs. Here, we reported HT-15, a prospective SGRM discovered by structure-based virtual screening (VS) and bioassays. HT-15 can selectively act on the NF-κB/AP1-mediated transrepression function of glucocorticoid receptor (GR) and repress the expression of pro-inflammation cytokines (i.e., IL-1β, IL-6, COX-2, and CCL-2) as effectively as dexamethasone (Dex). Compared with Dex, HT-15 shows less transactivation potency that is associated with the main adverse effects of synthetic GCs, and no cross activities with other nuclear receptors. Furthermore, HT-15 exhibits very weak inhibition on the ratio of OPG/RANKL. Therefore, it may reduce the side effects induced by normal GCs. The bioactive compound HT-15 can serve as a starting point for the development of novel therapeutics for high dose or long-term anti-inflammatory treatment.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10673}
}