ArticleJournal of cancer prevention2015
Selective Activator of the Glucocorticoid Receptor Compound A Dissociates Therapeutic and Atrophogenic Effects of Glucocorticoid Receptor Signaling in Skin.
Article in Journal of cancer prevention, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Trial
- Skin Anti-Inflammatory Potential with Reduced Side Effects of Novel Glucocorticoid Receptor Agonists.International journal of molecular sciences · 2023Article
- Synephrine and Its Derivative Compound A: Common and Specific Biological Effects.International journal of molecular sciences · 2023Review
- The long winding road to the safer glucocorticoid receptor (GR) targeting therapies.Oncotarget · 2022Review
- Multiple subcutaneous haematomas of the legs causing skin necrosis in an elderly patient affected by corticosteroid-induced skin atrophy: Case report and review of literature.International wound journal · 2020Review
- Glucocorticoid-Induced Skin Atrophy: The Old and the New.Clinical, cosmetic and investigational dermatology · 2020Review
- Transcriptomic Network Interactions in Human Skin Treated with Topical Glucocorticoid Clobetasol Propionate.The Journal of investigative dermatology · 2019Article
- GR Dimerization and the Impact of GR Dimerization on GR Protein Stability and Half-Life.Frontiers in immunology · 2019Review
- Novel role for receptor dimerization in post-translational processing and turnover of the GRα.Scientific reports · 2018Article
- Compound A influences gene regulation of the Dexamethasone-activated glucocorticoid receptor by alternative cofactor recruitment.Scientific reports · 2017Article
- Important role of kallikrein 6 for the development of keratinocyte proliferative resistance to topical glucocorticoids.Oncotarget · 2016Article
- Selective glucocorticoid receptor-activating adjuvant therapy in cancer treatments.Oncoscience · 2016Review
- Decoction ofPharmacognosy magazineArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundGlucocorticoids are effective anti-inflammatory drugs widely used in dermatology and for the treatment of blood cancer patients. Unfortunately, chronic treatment with glucocorticoids results in serious metabolic and atrophogenic adverse effects including skin atrophy. Glucocorticoids act via the glucocorticoid receptor (GR), a transcription factor that causes either gene transactivation (TA) or transrepression (TR). Compound A (CpdA), a novel non-steroidal GR ligand, does not promote GR dimerization and TA, retains anti-inflammatory potential but induces fewer metabolic side effects compared to classical glucocorticoids when used systemically. As topical effects of CpdA have not been well studied, this work goal was to compare the anti-inflammatory and side effects of topical CpdA and glucocorticoids and to assess their effect on GR TA and TR in keratinocytes.
methodsWe used murine immortalized keratinocytes and F1 C57BlxDBA mice. Effect of glucocorticoid fluocinolone acetonide (FA) and CpdA on gene expression in keratinocytes in vitro and in vivo was evaluated by reverse transcription-PCR. The anti-inflammatory effects were assessed in the model of tumor promoter 12-O-tertradecanoyl-acetate (TPA)-induced dermatitis and in croton oil-induced ear edema test. Skin atrophy was assessed by analysis of epidermal thickness, keratinocyte proliferation, subcutaneous adipose hypoplasia, and dermal changes after chronic treatment with FA and CpdA.
resultsIn mouse keratinocytes in vitro and in vivo, CpdA did not activate GR-dependent genes but mimicked closely the inhibitory effect of glucocorticoid FA on the expression of inflammatory cytokines and matrix metalloproteinases. When applied topically, CpdA inhibited TPA-induced skin inflammation and hyperplasia. Unlike glucocorticoids, CpdA itself did not induce skin atrophy which correlated with lack of induction of atrophogene regulated in development and DNA damage response 1 (REDD1) causatively involved in skin and muscle steroid-induced atrophy.
conclusionsOverall, our results suggest that CpdA and its derivatives represent novel promising class of anti-inflammatory compounds with reduced topical side effects.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.