Article
Chemistry, Multidisciplinary
Jin-ping Pang, Xue-ping Hu, Yun-xia Wang, Jia-ning Liao, Xin Chai, Xu-wen Wang, Chao Shen, Jia-jia Wang, Lu-lu Zhang, Xin-yue Wang, Feng Zhu, Qin-jie Weng, Lei Xu, Ting-jun Hou, Dan Li
Summary: Synthetic glucocorticoids (GCs) are commonly used for treating inflammatory diseases, but their side effects limit their use. Selective glucocorticoid receptor modulators (SGRMs) are expected to have fewer side effects. In this study, a potential SGRM HT-15 was discovered, which can effectively repress the expression of pro-inflammatory cytokines without causing the main adverse effects associated with synthetic GCs.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Pharmacology & Pharmacy
Yixuan Wang, Jian Gao, Ying Yu, Lin Zhou, Miao Wang, Wenwen Xue, Bo Liu, Xudong Wu, Xuefeng Wu, Huiyuan Gao, Yan Shen, Qiang Xu
Summary: Research has shown that CA-e is a selective glucocorticoid receptor modulator that can attenuate the side effects of glucocorticoid therapy and alleviate inflammation in multiple mouse models.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Haiyi Chen, Rui Zhou, Jinping Pang, Yue Guo, Jiawen Chen, Yu Kang, Mojie Duan, Tingjun Hou
Summary: This study explores the dissociation mechanisms of glucocorticoids and nonsteroidal ligands and discovers multiple dissociation pathways. Nonsteroidal ligands exhibit complex dissociation pathways, which are related to their interactions with surrounding residues. Additionally, the binding of ligands has a significant impact on the conformation of the hormone receptor and the homodimer interface, providing valuable insights for the design of novel anti-inflammatory drugs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Lisa Zeyen, Ole Morten Seternes, Ingvild Mikkola
Summary: The p38 MAPK pathway is important for cellular stress response. It regulates downstream effectors to control inflammation and cellular processes. Dysregulation of this pathway is associated with inflammatory diseases and cancer. Glucocorticoids (GCs) secretion is a classical endocrine response to stress and is regulated by the glucocorticoid receptor (GR). The crosstalk between p38 and GR plays a role in gene expression regulation and has potential clinical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Food Science & Technology
Yuan Liang, Qiuyan Jiang, Haoyang Zou, Jingqi Zhao, Jie Zhang, Li Ren
Summary: This study confirms that withaferin A can bind to glucocorticoid receptor (GR) and act as a potential selective GR modulator with anti-inflammatory effect. It inhibits the production of cytokines and decreases the expression of GR-related proteins, providing a basis for developing dietary supplements and nutraceuticals against inflammation.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Food Science & Technology
Jie Zhang, Jiarui Zhao, Yantong Sun, Yuan Liang, Jingqi Zhao, Haoyang Zou, Tiehua Zhang, Li Ren
Summary: Alpha-boswellic acid can bind to and translocate the glucocorticoid receptor (GR) but lacks transcriptional activity, making it a potential selective GR modulator against inflammatory disorders. It showed dissociative characteristics, separating transrepression from transactivation, and inhibited cytokine production, confirming its anti-inflammation property in vitro.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Chemistry, Medicinal
Susanne Prothon, Magnus Aurivillius, Ulrika Tehler, Ulf G. Eriksson, Ajay Aggarwal, Yingxue Chen
Summary: The study provides initial clinical evaluation of inhaled Velsecorat (AZD7594) for the treatment of asthma. The drug was found to be well tolerated with proportional plasma exposure to the dose and dose-dependent effects on markers of glucocorticoid activity.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Chemistry, Multidisciplinary
Xueping Hu, Jinping Pang, Jintu Zhang, Chao Shen, Xin Chai, Ercheng Wang, Haiyi Chen, Xuwen Wang, Mojie Duan, Weitao Fu, Lei Xu, Yu Kang, Dan Li, Hongguang Xia, Tingjun Hou
Summary: Different ligands binding to the glucocorticoid receptor (GR) can induce varying conformational changes and biological functions. This study explored the folding pathway of helix 12 (H12) induced by different ligands through molecular dynamics simulations and discovered a novel GR ligand, HP-19, with promising anti-inflammatory activity in the nuclear factor-kappa B signaling pathway and no adverse effects on GR transactivation functions.
Article
Immunology
Jose Garrido-Mesa, Bethan Lynne Thomas, John Dodd, Carl Spana, Mauro Perretti, Trinidad Montero-Melendez
Summary: This study demonstrated the therapeutic effects of MC1 agonist PL8177 in inflammatory conditions, including arthritis, showing both anti-inflammatory and pro-resolving activities. PL8177 activates MC1 to reduce clinical symptoms, swelling, and overall disease severity in a mouse model of inflammatory arthritis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Takafumi Kurimoto, Isao Tamai, Takashi Nakagawa, Atsuko Miyai, Yasuo Yamamoto, Yoshinori Kosugi, Katsuya Deai, Takahiro Hata, Takeshi Ohta, Mutsuyoshi Matsushita, Takahisa Yamada
Summary: JTP-117968, a novel selective glucocorticoid receptor modulator, demonstrates significant anti-inflammatory effects and reduced side effects in mouse models challenged with LPS and CIA, with lower impact on mouse femoral bone mineral density compared to other drugs.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Immunology
Andrew E. Greenstein, Hazel J. Hunt
Summary: Cortisol, an endogenous glucocorticoid receptor agonist, plays a regulatory role in various immune responses. In this study, the effects of endogenous cortisol on the anti-tumor immune response stimulated by immune checkpoint inhibitors were investigated. It was found that cortisol inhibited T-cell activation and pro-inflammatory cytokine secretion, while a selective glucocorticoid receptor modulator (SGRM) called relacorilant could restore these effects. Furthermore, combining relacorilant with an immune checkpoint inhibitor significantly improved the efficacy of anti-PD-1 antibody in tumor models.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Cell Biology
Steven Timmermans, Jolien Vandewalle, Claude Libert
Summary: This review paper provides an overview of the current knowledge and insights about the important aspect of glucocorticoid receptor (GR) biology, including the versatility of GR, its interactions with other proteins, the structural aspects of dimerization, and its impact on biological functions.
Article
Biochemistry & Molecular Biology
Yoshinori Takeuchi, Yuki Murayama, Yuichi Aita, Zahra Mehrazad Saber, Samia Karkoutly, Duhan Tao, Kyoka Katabami, Chen Ye, Akito Shikama, Yukari Masuda, Yoshihiko Izumida, Takafumi Miyamoto, Takashi Matsuzaka, Yasushi Kawakami, Hitoshi Shimano, Naoya Yahagi
Summary: This study reveals the mechanism by which the glucocorticoid receptor (GR) regulates hepatic lipogenesis through the KLF15-SREBP-1 pathway during fasting. It emphasizes the importance of the hypothalamic-pituitary-adrenal (HPA) axis-regulated GR-KLF15 pathway in the regulation of lipid metabolism in the liver during fasting.
Article
Neurosciences
Dominik Langgartner, Mascha Koenen, Sandra Kupfer, Lisa Glogger, Lisa Kurz, Luis Gustavo Perez-Rivas, Marily Theodoropoulou, Michael Noll-Hussong, Sabine Vettorazzi, Jan Tuckermann, Stefan O. Reber
Summary: Male C57BL/6N mice exposed to chronic psychosocial stress showed unaffected basal morning plasma corticosterone concentrations despite adrenal and pituitary hyperplasia and increased adrenocorticotropic hormone concentrations. However, these mice were still able to secrete increased corticosterone in response to novel stressors, suggesting an adaptation rather than a breakdown of the HPA axis. Using genetically modified mice, the study found that ACTH overexpression compromises adrenal adaptational processes during chronic stress exposure.
NEUROBIOLOGY OF STRESS
(2023)
Article
Endocrinology & Metabolism
Kan Wu, Zhihong Liu, Jiayu Liang, Fuxun Zhang, Fan Zhang, Yaohui Wang, Thongher Lia, Shenzhuo Liu, Yuchun Zhu, Xiang Li
Summary: This study aims to determine the clinical and biological significance of glucocorticoid receptor (GR) expression in adrenocortical carcinoma (ACC). The research findings suggest that low GR expression is significantly correlated with excess cortisol, immune signatures, and poor survival in ACC patients.
FRONTIERS IN ENDOCRINOLOGY
(2022)