ADORA2A (Adenosine A2a Receptor)

This robust activity was attributed to a dual mechanism combining immune stimulation and direct antiproliferative effects. These results make 13t a promising cancer immunotherapy drug candidate.

Although the pathway specificity and in vivo relevance require further studies, our findings provide evidence that PL-PN promotes extracellular matrix regeneration via coordinated proliferative, anabolic, and anti-inflammatory actions. Thus, PL-PN represents a potential sustainable plant-based alternative to S-PDRN for dermatological regeneration.

Adenosine attenuates the inflammatory activation of PVM/Ms and enhances their ability to maintain endothelial barrier integrity by binding to A2AR. The findings support adenosine and A2AR as potential therapeutic targets for treating hearing impairments.

Co-delivery of an ICD inducer (EPI) and an adenosine receptor antagonist (AB928) is realised in a stimuli-responsive nanomedicine to address immunosuppression induced by adenosine, thereby enhancing ICD effects and synergistically reprogramming the immunosuppressive tumor microenvironment.

This outcome is significantly superior to those of control groups lacking X-ray irradiation, SCH58261, or TM components. By integrating amplified RDT/CDT with blockade of A2AR, this study achieves concurrent induction of a localized ROS storm and immune reactivation, offering a novel therapeutic strategy for treatment-resistant glioma.

This combinatorial genetic disruption enhances CAR T cell effector function and anti-tumor efficacy leading to improved tumor elimination and survival in xenograft and humanized mouse solid tumor models. Our strategy confers CAR T cells resistance to multiple clinically relevant inhibitory signaling pathways that are amplified in hypoxic tumor areas and may improve the therapeutic potential of CAR T-cells against solid tumors.

At the protein level, BDNF enhanced TrkB expression at DIV 14 in an A2A receptor-dependent manner, without altering A2A receptor expression itself, further supporting a modulatory role of A2A receptors in BDNF receptor signalling. Overall, our results identify BDNF as a key regulator of OL differentiation and reveal an A2A receptor-BDNF interaction modulating this differentiation process.

However, unlike blinatumomab, which tends to induce T cell exhaustion, we showed that the release of PBF-509 from NanoBiTE suppressed the A2AR pathway and substantially improved tumor cell killing induced by NanoBiTE. Moreover, NanoBiTE treatment led to substantially reduced tumor burden in vivo in a humanized mouse model. Our results demonstrate that NanoBiTE is a safe and potent bispecific therapy that can also reduce T cell exhaustion for cancer immunotherapy.

Among all compounds tested, only the edaravone hybrid derivative P686 enhanced myelination in OPC/dorsal root ganglion neuron co-cultures, quantified by the Mander's coefficient which reflects the overlap between MBP+-pixels and the neuronal marker βIII-tubulin+-pixels. These findings results provide mechanistic insight into how multitarget modulation of A2A receptor signalling and oxidative stress regulates oligodendrocyte differentiation and myelination, highlighting avenues for future studies rather than therapeutic application in supportthe potential of multitarget compounds as promising therapeutic candidates for the treatment of demyelinating diseases.

This review provides an integrated analysis of A2AAR and A2BAR functions across immune and stromal compartments, summarizes current selective antagonists (A2AAR and A2BAR) and dual antagonists, and highlights compounds in clinical studies. Moreover, it discusses synergistic combination strategies that integrate adenosine blockade with complementary immunotherapeutic and conventional approaches to enhance antitumor responses.

Integration with anti-PD-L1 therapy (αPD-L1) achieved complete tumor regression in 60% of the treated mice-bearing orthotopic hepatocellular carcinoma. These findings establish a paradigm-shifting strategy for reprogramming tumor-immune metabolic checkpoints using strain-engineered nanocatalytic probiotics, thereby enhancing iRT and overcoming radioresistance.

Furthermore, overexpression of PNP or using taminadenant, a A2aR-targeting inhibitor used in clinical trials, significantly enhances the EGFR-targeted therapeutic response in vitro, as well as in patient-derived organoids, cell-derived xenografts and mouse models bearing human EGFR-driven spontaneous lung tumor. Overall, our findings clarify the role of inosine metabolism in TKI resistance, highlighting a potential therapeutic strategy-targeting the inosine/A2aR axis-to counteract EGFR-TKI tolerance in LUAD treatment.