Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological Implications
The development of GPCR (G-coupled protein receptor) allosteric modulators has attracted increasing interest in the last decades. The use of allosteric modulators in therapy offers several advantages with respect to orthosteric ones, as they can fine-tune the tissue responses to the endogenous agoni...
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doaj-a7ed00e82d514b68ba58277e6f5280ad2021-03-24T04:58:18ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-03-011210.3389/fphar.2021.652121652121Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological ImplicationsElisabetta Barresi0Claudia Martini1Federico Da Settimo2Giovanni Greco3Sabrina Taliani4Chiara Giacomelli5Maria Letizia Trincavelli6Department of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Naples, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyThe development of GPCR (G-coupled protein receptor) allosteric modulators has attracted increasing interest in the last decades. The use of allosteric modulators in therapy offers several advantages with respect to orthosteric ones, as they can fine-tune the tissue responses to the endogenous agonist. Since the discovery of the first A1 adenosine receptor (AR) allosteric modulator in 1990, several efforts have been made to develop more potent molecules as well as allosteric modulators for all adenosine receptor subtypes. There are four subtypes of AR: A1, A2A, A2B, and A3. Positive allosteric modulators of the A1 AR have been proposed for the cure of pain. A3 positive allosteric modulators are thought to be beneficial during inflammatory processes. More recently, A2A and A2B AR allosteric modulators have also been disclosed. The A2B AR displays the lowest affinity for its endogenous ligand adenosine and is mainly activated as a consequence of tissue damage. The A2B AR activation has been found to play a crucial role in chronic obstructive pulmonary disease, in the protection of the heart from ischemic injury, and in the process of bone formation. In this context, allosteric modulators of the A2B AR may represent pharmacological tools useful to develop new therapeutic agents. Herein, we provide an up-to-date highlight of the recent findings and future perspectives in the field of orthosteric and allosteric A2B AR ligands. Furthermore, we compare the use of orthosteric ligands with positive and negative allosteric modulators for the management of different pathological conditions.https://www.frontiersin.org/articles/10.3389/fphar.2021.652121/fulladenosine receptorsallosteric modulatorsA2B receptormesenchymal stromal cellsbone healing |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elisabetta Barresi Claudia Martini Federico Da Settimo Giovanni Greco Sabrina Taliani Chiara Giacomelli Maria Letizia Trincavelli |
spellingShingle |
Elisabetta Barresi Claudia Martini Federico Da Settimo Giovanni Greco Sabrina Taliani Chiara Giacomelli Maria Letizia Trincavelli Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological Implications Frontiers in Pharmacology adenosine receptors allosteric modulators A2B receptor mesenchymal stromal cells bone healing |
author_facet |
Elisabetta Barresi Claudia Martini Federico Da Settimo Giovanni Greco Sabrina Taliani Chiara Giacomelli Maria Letizia Trincavelli |
author_sort |
Elisabetta Barresi |
title |
Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological Implications |
title_short |
Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological Implications |
title_full |
Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological Implications |
title_fullStr |
Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological Implications |
title_full_unstemmed |
Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological Implications |
title_sort |
allosterism vs. orthosterism: recent findings and future perspectives on a2b ar physio-pathological implications |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-03-01 |
description |
The development of GPCR (G-coupled protein receptor) allosteric modulators has attracted increasing interest in the last decades. The use of allosteric modulators in therapy offers several advantages with respect to orthosteric ones, as they can fine-tune the tissue responses to the endogenous agonist. Since the discovery of the first A1 adenosine receptor (AR) allosteric modulator in 1990, several efforts have been made to develop more potent molecules as well as allosteric modulators for all adenosine receptor subtypes. There are four subtypes of AR: A1, A2A, A2B, and A3. Positive allosteric modulators of the A1 AR have been proposed for the cure of pain. A3 positive allosteric modulators are thought to be beneficial during inflammatory processes. More recently, A2A and A2B AR allosteric modulators have also been disclosed. The A2B AR displays the lowest affinity for its endogenous ligand adenosine and is mainly activated as a consequence of tissue damage. The A2B AR activation has been found to play a crucial role in chronic obstructive pulmonary disease, in the protection of the heart from ischemic injury, and in the process of bone formation. In this context, allosteric modulators of the A2B AR may represent pharmacological tools useful to develop new therapeutic agents. Herein, we provide an up-to-date highlight of the recent findings and future perspectives in the field of orthosteric and allosteric A2B AR ligands. Furthermore, we compare the use of orthosteric ligands with positive and negative allosteric modulators for the management of different pathological conditions. |
topic |
adenosine receptors allosteric modulators A2B receptor mesenchymal stromal cells bone healing |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.652121/full |
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