Structure-based drug design of chromone antagonists of the adenosine A2A receptor

MedChemComm ◽  
2014 ◽  
Vol 5 (5) ◽  
pp. 571-575 ◽  
Author(s):  
Stephen P. Andrews ◽  
Jonathan S. Mason ◽  
Edward Hurrell ◽  
Miles Congreve
Keyword(s):  
Drug Design ◽  
Adenosine A2a Receptor ◽  
Structure Based Drug Design ◽  
A2a Receptor ◽  
Adenosine A2a

Structure-based drug design identifies potent & selective GPCR antagonists.

Stabilised G protein-coupled receptors in structure-based drug design: a case study with adenosine A2A receptor

MedChemComm ◽  
2013 ◽  
Vol 4 (1) ◽  
pp. 52-67 ◽  
Author(s):  
Stephen P. Andrews ◽  
Benjamin Tehan
Keyword(s):  
Parkinson’S Disease ◽  
Drug Design ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Adenosine A2a Receptor ◽  
Structure Based Drug Design ◽  
A2a Receptor ◽  
Adenosine A2a ◽  
G Protein Coupled

The first example of structure-based drug design with stabilised GPCRs has enabled the identification of a preclinical candidate for the treatment of Parkinson's disease.

Synthesis of the Adenosine A2A Receptor Fluorescent Agonist MRS5424

BIO-PROTOCOL ◽  
2014 ◽  
Vol 4 (6) ◽  
Author(s):  
Kenneth Jacobson ◽  
Francisco Ciruela
Keyword(s):  
Adenosine A2a Receptor ◽  
A2a Receptor ◽  
Adenosine A2a

Optimization of the Human Adenosine A2a Receptor Yields in Saccharomyces cerevisiae

2008 ◽  
Vol 22 (5) ◽  
pp. 1249-1255 ◽  
Author(s):  
Alison Wedekind ◽  
Michelle A. O'Malley ◽  
Ronald T. Niebauer ◽  
Anne S. Robinson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Adenosine A2a Receptor ◽  
A2a Receptor ◽  
Adenosine A2a

scholarly journals A Cellular Assay for the Identification and Characterization of Connexin Gap Junction Modulators

2021 ◽  
Vol 22 (3) ◽  
pp. 1417
Author(s):  
Azeem Danish ◽  
Robin Gedschold ◽  
Sonja Hinz ◽  
Anke C. Schiedel ◽  
Dominik Thimm ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Small Molecules ◽  
High Throughput Screening ◽  
Cell Communication ◽  
Receptor Activation ◽  
Adenosine A2a Receptor ◽  
Intracellular Camp ◽  
Donor Cells ◽  
A2a Receptor ◽  
Adenosine A2a

Connexin gap junctions (Cx GJs) enable the passage of small molecules and ions between cells and are therefore important for cell-to-cell communication. Their dysfunction is associated with diseases, and small molecules acting as modulators of GJs may therefore be useful as therapeutic drugs. To identify GJ modulators, suitable assays are needed that allow compound screening. In the present study, we established a novel assay utilizing HeLa cells recombinantly expressing Cx43. Donor cells additionally expressing the Gs protein-coupled adenosine A2A receptor, and biosensor cells expressing a cAMP-sensitive GloSensor luciferase were established. Adenosine A2A receptor activation in the donor cells using a selective agonist results in intracellular cAMP production. The negatively charged cAMP migrates via the Cx43 gap junctions to the biosensor cells and can there be measured by the cAMP-dependent luminescence signal. Cx43 GJ modulators can be expected to impact the transfer of cAMP from the donor to the biosensor cells, since cAMP transit is only possible via GJs. The new assay was validated by testing the standard GJ inhibitor carbenoxolon, which showed a concentration-dependent inhibition of the signal and an IC50 value that was consistent with previously reported values. The assay was demonstrated to be suitable for high-throughput screening.

scholarly journals Correlation between low adenosine A2A receptor expression and hypercholesterolemia: A new component of the cardiovascular risk?

2021 ◽  
Vol 1866 (2) ◽  
pp. 158850
Author(s):  
Donato Vairo ◽  
Carola Giacobbe ◽  
Claire Guiol ◽  
Marie-Charlotte Chaptal ◽  
Maria Donata Di Taranto ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Adenosine A2a Receptor ◽  
Receptor Expression ◽  
A2a Receptor ◽  
Adenosine A2a

scholarly journals Adenosine A2A receptor signaling promotes FoxO associated autophagy in chondrocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin Friedman ◽  
Carmen Corciulo ◽  
Cristina M. Castro ◽  
Bruce N. Cronstein
Keyword(s):  
Cell Line ◽  
Metabolic Stress ◽  
Human Cell Line ◽  
Adenosine A2a Receptor ◽  
Autophagic Flux ◽  
A2a Receptor ◽  
Adenosine A2a ◽  
A2ar Agonist

AbstractAutophagy, a homeostatic pathway upregulated during cellular stress, is decreased in osteoarthritic chondrocytes and this reduction in autophagy is thought to contribute to the development and progression of osteoarthritis (OA). The adenosine A2A receptor (A2AR) is a potent anti-inflammatory receptor and deficiency of this receptor leads to the development of OA in mice. Moreover, treatment using liposomally conjugated adenosine or a specific A2AR agonist improved joint scores significantly in both rats with post-traumatic OA (PTOA) and mice subjected to a high fat diet obesity induced OA. Importantly, A2AR ligation is beneficial for mitochondrial health and metabolism in vitro in primary and the TC28a2 human cell line. An additional set of metabolic, stress-responsive, and homeostatic mediators include the Forkhead box O transcription factors (FoxOs). Data has shown that mouse FoxO knockouts develop early OA with reduced cartilage autophagy, indicating that FoxO-induced homeostasis is important for articular cartilage. Given the apparent similarities between A2AR and FoxO signaling, we tested the hypothesis that A2AR stimulation improves cartilage function through activation of the FoxO proteins leading to increased autophagy in chondrocytes. We analyzed the signaling pathway in the human TC28a2 cell line and corroborated these findings in vivo in a metabolically relevant obesity-induced OA mouse model. We found that A2AR stimulation increases activation and nuclear localization of FoxO1 and FoxO3, promotes an increase in autophagic flux, improves metabolic function in chondrocytes, and reduces markers of apoptosis in vitro and reduced apoptosis by TUNEL assay in vivo. A2AR ligation additionally enhances in vivo activation of FoxO1 and FoxO3 with evidence of enhanced autophagic flux upon injection of the liposome-associated A2AR agonist in a mouse obesity-induced OA model. These findings offer further evidence that A2AR may be an excellent target for promoting chondrocyte and cartilage homeostasis.

scholarly journals Adenosine A2A receptor null chondrocyte transcriptome resembles that of human osteoarthritic chondrocytes

2021 ◽  
Author(s):  
Cristina M. Castro ◽  
Carmen Corciulo ◽  
Benjamin Friedman ◽  
Zhi Li ◽  
Samson Jacob ◽  
...  
Keyword(s):  
Adenosine A2a Receptor ◽  
Osteoarthritic Chondrocytes ◽  
A2a Receptor ◽  
Adenosine A2a
Sign in / Sign up

Export Citation Format

Share Document