BAY 60-6583 is a High-Affinity and Specific Adenosine A2B Receptor Agonist

BAY 60-6583 is a High-Affinity and Specific Adenosine A2B Receptor Agonist

In this article, we will introduce a potent and high-affinity agonist of adenosine A2B receptor, BAY 60-6583. BAY 60-6583 exhibits high affinity by binds to mouse, rabbit, and dog A2BAR with Ki values of  750nM, 340 nM and 330 nM, respectively.

BAY 60 6583 is a High Affinity and Specific Adenosine A 2B Receptor Agonist 2020 01 14 - BAY 60-6583 is a High-Affinity and Specific Adenosine A<sub>2B</sub> Receptor Agonist

We will describe this compound in vitro and in vivo.

Firstly, in vitro, in CHO cells expressing recombinant human A1, A2A or A2B ARs, BAY 60-6583 exhibits EC50 values for receptor activation >10 μM for both A1 and A2A AR and 3 nM for A2B AR subtype.

In T24 cells, at a concentration of 0-10 µM, BAY 60-6583 exhibits the maximum agonist effect of BAY in the absence of siRNA is 68 %. Meanwhile, BAY 60-6583 exhibits EC50 values of BAY in the absence and presence of siRNA with 98, 102, 127 and 93 nM, respectively.

Secondly, in RAW264.7 preosteoclasts, BAY 60-6583 can induce cell-cycle arrest. Additionally, it increases the accumulation of cells at the G1 phase with a decrease in G2/M phase. Additionally, BAY 60-6583 specifically inhibits the activation of Akt by M-CSF, whereas M-CSF-induced ERK1/2 activation is not affected by BAY 60-6583 treatment.

Lastly, in vivo studies will be precisely introduced here.

BAY 60-6583 (100 mcg/kg) can reduce the infarction area just before reperfusion in ischaemic rabbit hearts by intravenous injection.

pre-treatment with BAY 60-6583 can significantly decrease LPS-increased IL-6 levels and attenuate LPS-induced lung injury in WT mice. In contrast, in A2BAR−/− mice, BAY 60-6583 treatment is ineffective in abrogating these inflammatory parameters.

In female C57Bl6j and Athymic Nude-Foxn1nu mice, BAY 60-6583 promotes melanoma growth by inducing an immune-suppressive environment in the tumor tissue. This compound causes a significant increase in tumor-infiltrating MDSCs. However, it does not affect either their ability to suppress T-cell proliferation nor their degree of maturation. At the same time, it stimulates the production of IL-10 and CCL2 in the tumor tissue.

In summary, BAY 60-6583 is a potent and highly selective A2BAR  agonist. It exhibits a high affinity to A2BAR in vitro and in vivo. BAY 60-6583 has a cardioprotective effect in a myocardial ischemia model. However, it promotes melanoma growth by inducing an immune-suppressive environment in mice.

 

Reference:

Aherne CM, et al.Mucosal Immunol. 2015 Nov;8(6):1324-38.

Yoon Taek Oh, et al. Biomed Sci Letters 2017;23:194-200

 

 

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