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- W3124036045 abstract "Glucocorticoids display remarkable anti-inflammatory activity, but their use is limited by on-target adverse effects including insulin resistance and skeletal muscle atrophy. We used a chemical systems biology approach, ligand class analysis, to examine ligands designed to modulate glucocorticoid receptor activity through distinct structural mechanisms. These ligands displayed diverse activity profiles, providing the variance required to identify target genes and coregulator interactions that were highly predictive of their effects on myocyte glucose disposal and protein balance. Their anti-inflammatory effects were linked to glucose disposal but not muscle atrophy. This approach also predicted selective modulation in vivo, identifying compounds that were muscle-sparing or anabolic for protein balance and mitochondrial potential. Ligand class analysis defined the mechanistic links between the ligand–receptor interface and ligand-driven physiological outcomes, a general approach that can be applied to any ligand-regulated allosteric signaling system. A systems-based approach to profile glucocorticoid (GC) receptor ligands in a broad range of assays representing different phenotypic responses linked these to transcriptional profiles and led to separation of GC therapeutic effects from side effects." @default.
- W3124036045 created "2021-02-01" @default.
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- W3124036045 date "2021-01-28" @default.
- W3124036045 modified "2023-10-09" @default.
- W3124036045 title "Chemical systems biology reveals mechanisms of glucocorticoid receptor signaling" @default.
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- W3124036045 doi "https://doi.org/10.1038/s41589-020-00719-w" @default.
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