CGS 21680

Conversely, the pretreatment with CGS21680 in vivo and in vitro showed corresponding improvement in functions of vascular endothelial dysfunction. These data demonstrate that A2aR in macrophages represents a promising novel therapeutic target for LPS-induced uncontrolled vascular endothelial injury and inflammation potentially through reducing macrophage M1 polarisation and OS and inhibiting the production and release of TNF-α production.

Using B cells derived from peripheral blood, the A2AR agonist CGS-21680 was shown to inhibit the maturation of B cells into plasma cells, and that maturation could be fully restored by inupadenant. This is in line with recent reports showing that B cells, plasma cells and tertiary lymphoid structures are associated with favorable responses to cancer immunotherapy. Interestingly, four out of the five non-progressors treated with inupadenant as monotherapy and with available biomarker data showed a reduction in ASC infiltration after inupadenant treatment, suggesting that inupadenant may promote terminal plasma cell differentiation and migration out of the tumor tissue and to the bone marrow.Altogether, these data support a novel plasma cell-centric mechanism of action of inupadenant, which may complement its reported T cell-mediated anti-tumor activity.

Theacrine was further demonstrated to be an effective antagonist of the adenosine 2A receptor as its concurrent supplementation significantly reduced the elevation of AMPK phosphorylation level in MCF-7 human breast cells induced by CGS21680, an agonist of adenosine 2A receptors...Similar to the caffeine, significant elevation of interferon-γ and tumor necrosis factor-α was observed in the serum and tumor tissues of rats after the theacrine supplement of 50 mg/kg body weight. Taken together, theacrine is an effective antagonist of adenosine 2A receptors and possesses great potential to be used to attenuate breast cancer.