TY - JOUR
T1 - Medicinal chemistry of a 2B adenosine receptors
AU - Müller, Christa E.
AU - Baqi, Younis
AU - Hinz, Sonja
AU - Namasivayam, Vigneshwaran
N1 - Publisher Copyright:
© Springer Nature Switzerland AG 2018.
PY - 2018
Y1 - 2018
N2 - A 2B adenosine receptors (A 2B ARs) are in the focus of interest as drug targets in (immuno)oncology since antagonists show anti-proliferative, anti-angiogenic, anti-metastatic, and immunostimulatory properties. Additional (poten-tial) indications for A 2B AR antagonists include inflammatory (pulmonary, colon) and autoimmune diseases, pain, fibrosis, infectious diseases, diabetes, and more. Agonists were found to exhibit cardioprotective properties. The A 2B AR is most closely related to the A 2A AR subtype. Both are G s protein-coupled receptors, but the A 2B AR is additionally coupled to G q proteins. A 2B AR expression is upregulated under pathological conditions (hypoxia, inflammation, ischemia) and on many cancer cells. A 2B ARs form stable heteromeric complexes with A 2A ARs when co-expressed, and thereby completely block A 2A AR signaling. There is still a lack of potent, selective, and fully efficacious A 2B AR agonists, while structurally diverse potent and selective competitive antagonists for A 2B ARs have become available. The first positive and negative allosteric modulators for A 2B ARs were recently described. For the labeling of A 2B ARs, antagonist radioligands have been developed, and recently the first potent and selective fluorescent ligands were reported.
AB - A 2B adenosine receptors (A 2B ARs) are in the focus of interest as drug targets in (immuno)oncology since antagonists show anti-proliferative, anti-angiogenic, anti-metastatic, and immunostimulatory properties. Additional (poten-tial) indications for A 2B AR antagonists include inflammatory (pulmonary, colon) and autoimmune diseases, pain, fibrosis, infectious diseases, diabetes, and more. Agonists were found to exhibit cardioprotective properties. The A 2B AR is most closely related to the A 2A AR subtype. Both are G s protein-coupled receptors, but the A 2B AR is additionally coupled to G q proteins. A 2B AR expression is upregulated under pathological conditions (hypoxia, inflammation, ischemia) and on many cancer cells. A 2B ARs form stable heteromeric complexes with A 2A ARs when co-expressed, and thereby completely block A 2A AR signaling. There is still a lack of potent, selective, and fully efficacious A 2B AR agonists, while structurally diverse potent and selective competitive antagonists for A 2B ARs have become available. The first positive and negative allosteric modulators for A 2B ARs were recently described. For the labeling of A 2B ARs, antagonist radioligands have been developed, and recently the first potent and selective fluorescent ligands were reported.
KW - A adenosine receptor
KW - Agonist
KW - Antagonist
KW - Cancer
KW - Inflammation
KW - Structure
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U2 - 10.1007/978-3-319-90808-3_6
DO - 10.1007/978-3-319-90808-3_6
M3 - Article
AN - SCOPUS:85052243403
SN - 1048-6909
VL - 34
SP - 137
EP - 168
JO - Receptors
JF - Receptors
ER -