PMID- 32982485
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1179-1454 (Print)
IS  - 1179-1454 (Electronic)
IS  - 1179-1454 (Linking)
VI  - 12
DP  - 2020
TI  - Experimental Glucocorticoid Receptor Agonists for the Treatment of Asthma: A 
      Systematic Review.
PG  - 233-254
LID - 10.2147/JEP.S237480 [doi]
AB  - Inhaled corticosteroids (ICSs) are considered the cornerstone of asthma 
      treatment. Despite the solid evidence documenting the efficacy and safety of ICSs 
      at the level of the airways, their use can be affected by pulmonary and systemic 
      adverse events (AEs) when administered chronically and/or at high doses. Thus, 
      there is a pharmacological and medical need for new glucocorticoid (GC) receptor 
      (GR) ligands with a more favorable therapeutic index, in order to overcome the 
      shortcomings of currently available ICSs. The therapeutic profile of GCs can be 
      improved by enhancing genomic mechanisms mediated by transrepression, which is 
      assumed to be responsible for several anti-inflammatory and immunomodulatory 
      actions, rather than transactivation, which causes most of the GC-associated AEs. 
      It was assumed that an independent modulation of the molecular mechanisms 
      underlying transactivation and transrepression could translate into the 
      dissociation of beneficial effects from AEs. Therefore, current research is 
      looking for GCs that are able to elicit prevalently transrepression with 
      negligible transactivating activity. These compounds are known as selective 
      glucocorticoid receptor agonists (SEGRAs). In this review, experimental GR 
      agonists currently in pre-clinical and clinical development for the treatment of 
      asthma have been systematically assessed. Several compounds are currently under 
      pre-clinical development, but only three novel experimental GR agonists 
      (GW870086X, AZD5423, AZD7594) seem to have some potential therapeutic relevance 
      and have entered clinical trials for the treatment of asthma. Since data from 
      pre-clinical studies have not always been confirmed in clinical investigations, 
      well-designed randomized controlled trials are needed in asthmatic patients to 
      confirm the potentially positive benefit/risk ratio of each specific SEGRA and to 
      optimize the development strategy of these agents in respiratory medicine.
CI  - (c) 2020 Rogliani et al.
FAU - Rogliani, Paola
AU  - Rogliani P
AUID- ORCID: 0000-0001-7801-5040
AD  - Unit of Respiratory Medicine, Department of Experimental Medicine, University of 
      Rome "Tor Vergata", Rome, Italy.
AD  - Division of Respiratory Medicine, University Hospital "Tor Vergata", Rome, Italy.
FAU - Ritondo, Beatrice Ludovica
AU  - Ritondo BL
AD  - Unit of Respiratory Medicine, Department of Experimental Medicine, University of 
      Rome "Tor Vergata", Rome, Italy.
FAU - Puxeddu, Ermanno
AU  - Puxeddu E
AD  - Division of Respiratory Medicine, University Hospital "Tor Vergata", Rome, Italy.
FAU - Pane, Gloria
AU  - Pane G
AD  - Division of Respiratory Medicine, University Hospital "Tor Vergata", Rome, Italy.
FAU - Cazzola, Mario
AU  - Cazzola M
AUID- ORCID: 0000-0003-4895-9707
AD  - Unit of Respiratory Medicine, Department of Experimental Medicine, University of 
      Rome "Tor Vergata", Rome, Italy.
FAU - Calzetta, Luigino
AU  - Calzetta L
AUID- ORCID: 0000-0003-0456-069X
AD  - Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, 
      University of Parma, Parma, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200806
PL  - New Zealand
TA  - J Exp Pharmacol
JT  - Journal of experimental pharmacology
JID - 101530345
PMC - PMC7495344
OTO - NOTNLM
OT  - SEGRA
OT  - asthma
OT  - efficacy
OT  - glucocorticoid agonists
OT  - safety
COIS- PR reports grants and personal fees from Boehringer Ingelheim, grants and 
      personal fees from Novartis, personal fees from AstraZeneca, grants and personal 
      fees from Chiesi Farmaceutici, grants and personal fees from Almirall, grants 
      from Zambon, personal fees from Biofutura, personal fees from GlaxoSmithKline, 
      personal fees from Menarini, and personal fees from Mundipharma. MC has 
      participated as a faculty member and advisor in scientific meetings and courses 
      under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, 
      Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, 
      Novartis, Pfizer, Verona Pharma, and Zambon; is or has been a consultant to ABC 
      Farmaceutici, AstraZeneca, Chiesi Farmaceutici, Edmond Pharma, Lallemand, 
      Novartis, Ockham Biotech, Verona Pharma, and Zambon, and his department was 
      funded by Almirall. LC reports grants and personal fees from Boehringer 
      Ingelheim, grants and personal fees from Novartis, nonfinancial support from 
      AstraZeneca, grants from Chiesi Farmaceutici, grants from Almirall, personal fees 
      from ABC Farmaceutici, personal fees from Edmond Pharma, grants and personal fees 
      from Zambon, personal fees from Verona Pharma, and personal fees from Ockham 
      Biotech. The authors report no other conflicts of interest in this work.
EDAT- 2020/09/29 06:00
MHDA- 2020/09/29 06:01
PMCR- 2020/08/06
CRDT- 2020/09/28 05:38
PHST- 2020/05/05 00:00 [received]
PHST- 2020/07/02 00:00 [accepted]
PHST- 2020/09/28 05:38 [entrez]
PHST- 2020/09/29 06:00 [pubmed]
PHST- 2020/09/29 06:01 [medline]
PHST- 2020/08/06 00:00 [pmc-release]
AID - 237480 [pii]
AID - 10.2147/JEP.S237480 [doi]
PST - epublish
SO  - J Exp Pharmacol. 2020 Aug 6;12:233-254. doi: 10.2147/JEP.S237480. eCollection 
      2020.