Uses
BAY 60-6583 is a potent and selective adenosine A2B receptor agonist. BAY 60-6583 shows protective effects against ischemia in both the heart and kidney in animal models. BAY 60-6583 is also a useful therapeutic drug in the treatment of acute lung injury.
Definition
ChEBI: A member of the class of cyanopyridines that is 6-amino-3,5-dicyano-4-(4-hydroxyphenyl)-2-sulfanylpyridine in which the hydroxy and sulfanyl hydrogens are replaced by cyclopropylmethyl and carboxamidomethyl groups respectively.
Biological Activity
bay 60-6583 is a selective and potent agonist of adenosine a2b receptor with ec50 value of 3 nm [1].the adenosine a2b receptor is a g-protein coupled adenosine receptor and is activated by high concentrations adenosine. the adenosine a2b receptor plays an important role in anti-inflammatory response and pre/postconditioning cardioprotective [1].bay 60-6583 is a potent adenosine a2b receptor agonist. in cho cells, bay 60-6583 showed ec50 values of >10000, >10000 and 3 nm respectively for recombinant human a1, a2a and a2b ars [1]. in beas-2b human airway epithelial cells transfected with glucocorticoid response element (gre) reporter and camp-response element (cre), bay 60-6583 increased gre- and cre-dependent transcription mediated by adenosine a2b receptor that was associated with camp formation. also, bay 60-6583 increased the expression of cd200, crispld2 and socs3, which suppressed the release of proinflammatory mediator [2]. in macrophages derived from arterial injury mice, bay 60-6583 increased the expression of a2bar, which then inhibited the released of tumor necrosis factor ɑ (tnf-ɑ) that promoting inflammatory response [3].in a myocardial ischaemic injury rabbit model, bay 60-6583 (100 mcg/kg) reduced the infarction area [1].
in vivo
BAY 60-6583 (intravenous injection; 100 mcg/kg) reduces the infarction area just prior to reperfusion in ischaemic rabbit hearts[1].
BAY 60-6583 (intraperitoneal injection; 2 mg/kg) attenuates LPS-induced lung injury, pre-treatment with this compound can significantly decrease LPS-increased IL-6 levels in WT-mice, In contrast, BAY 60-6583 treatment is ineffective in abrogating these inflammatory parameters in A2BAR mice[2].
BAY 60-6583 (intratumoral administration) causes a significant increase in tumor-infiltrating MDSCs, it does not affect neither their ability to suppress T-cell proliferation nor their degree of maturation, it also stimulates the production of IL-10 and CCL2 in the tumor tissue[5].
| Animal Model: | ?A2BAR?/? ?mice on a C57BL/6J mice[1] |
| Dosage: | 2 mg/kg |
| Administration: | Intraperitoneal?injection; 2 mg/kg |
| Result: | Demonstrated attenuation of lung inflammation and pulmonary edema in wild-type but not in gene-targeted mice for the A2BAR. |
References
[1]. baraldi pg, tabrizi ma, fruttarolo f, et al. recent improvements in the development of a(2b) adenosine receptor agonists. purinergic signal, 2008, 4(4): 287-303.
[2]. greer s, page cw, joshi t, et al. concurrent agonism of adenosine a2b and glucocorticoid receptors in human airway epithelial cells cooperatively induces genes with anti-inflammatory potential: a novel approach to treat chronic obstructive pulmonary disease. j pharmacol exp ther, 2013, 346(3): 473-485.
[3]. chen h, yang d, carroll sh, et al. activation of the macrophage a2b adenosine receptor regulates tumor necrosis factor-alpha levels following vascular injury. exp hematol, 2009, 37(5): 533-538.
