ArticleProceedings of the National Academy of Sciences of the United States of America2019
The glucocorticoid receptor agonistic modulators CpdX and CpdX-D3 do not generate the debilitating effects of synthetic glucocorticoids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Selective Glucocorticoid Receptor Modulators (SEGRAMs): Can They Improve the Therapeutic Index of Steroid Therapy?Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Targeting nuclear receptors in muscular dystrophies and regenerative myogenesis.Frontiers in cell and developmental biology · 2026Review
- Anti-Cancer Outcome of Glucocorticoid Receptor Transrepression by Synephrine Derivatives in Hematological Malignancies.International journal of molecular sciences · 2025Article
- A cross-tissue transcriptomic approach decodes glucocorticoid receptor-dependent links to human metabolic phenotypes.BMC genomics · 2025Article
- Targeting glucocorticoid receptor signaling pathway for treatment of stress-related brain disorders.Pharmacological reports : PR · 2024Review
- Synthesis and Anti-Cancer Activity of the Novel Selective Glucocorticoid Receptor Agonists of the Phenylethanolamine Series.International journal of molecular sciences · 2024Article
- LSD1 inhibition circumvents glucocorticoid-induced muscle wasting of male mice.Nature communications · 2024Article
- Ipriflavone as a non-steroidal glucocorticoid receptor antagonist ameliorates diabetic cognitive impairment in mice.Aging cell · 2022Article
- The long winding road to the safer glucocorticoid receptor (GR) targeting therapies.Oncotarget · 2022Review
- Review
- Local steroid activation is a critical mediator of the anti-inflammatory actions of therapeutic glucocorticoids.Annals of the rheumatic diseases · 2021Article
- Mechanisms and Clinical Applications of Glucocorticoid Steroids in Muscular Dystrophy.Journal of neuromuscular diseases · 2021Review
- Caffeoyl-Prolyl-Histidine Amide Inhibits Fyn and Alleviates Atopic Dermatitis-Like Phenotypes via Suppression of NF-κB Activation.International journal of molecular sciences · 2020Article
- Definition of functionally and structurally distinct repressive states in the nuclear receptor PPARγ.Nature communications · 2019Article
- Glucocorticoid receptor modulators CpdX and CpdX-D3 exhibit the same in vivo antiinflammatory activities as synthetic glucocorticoids.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Seventy years after the discovery of their anti-inflammatory properties, glucocorticoids (GCs) remain the mainstay treatment for major allergic and inflammatory disorders, such as atopic dermatitis, asthma, rheumatoid arthritis, colitis, and conjunctivitis, among others. However, their long-term therapeutical administration is limited by major debilitating side effects, e.g., skin atrophy, osteoporosis, Addison-like adrenal insufficiency, fatty liver, and type 2 diabetes syndrome, as well as growth inhibition in children. These undesirable side effects are mostly related to GC-induced activation of both the direct transactivation and the direct transrepression functions of the GC receptor (GR), whereas the activation of its GC-induced indirect tethered transrepression function results in beneficial anti-inflammatory effects. We have reported in the accompanying paper that the nonsteroidal compound CpdX as well as its deuterated form CpdX-D3 selectively activate the GR indirect transrepression function and are as effective as synthetic GCs at repressing inflammations generated in several mouse models of major pathologies. We now demonstrate that these CpdX compounds are bona fide selective GC receptor agonistic modulators (SEGRAMs) as none of the known GC-induced debilitating side effects were observed in the mouse upon 3-mo CpdX treatments. We notably report that, unlike that of GCs, the administration of CpdX to ovariectomized (OVX) mice does not induce a fatty liver nor type 2 diabetes, which indicates that CpdX could be used in postmenopausal women as an efficient "harmless" GC substitute.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.