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ADORA2A

Products

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

ADORA2a is a Class A rhodopsin-like G protein-coupled receptor family and is an archetypal member of the purinergic P1 receptor family and preferential coupling to heterotrimeric Gs protein (GS). After agonist engagement, GS stimulates adenylyl cyclase, which increases intracellular cyclic AMP that then activates protein kinase A-dependent signaling cascades. When in vivo and under physiological conditions, low extracellular adenosine concentrations and ADORA2A signaling mediate biologic activities like coronary vasodilation, neuronal modulation or synaptic transmission tuning. In stark contrast, in pathological microenvironments—tissues challenged by inflammation or ischemia, degenerating neural circuits—the levels of adenosine will saturate below the micromolar scale at organismal dimensions, converting ADORA2A into a potent suppressive switch. Adenosine, driven by tumor hypoxia engages ADORA2A as a non-redundant immune checkpoint (beyond PD-1/CTLA-4) that activates cAMP-mediated inhibition of cytokine production and release of lytic granules from infiltrating cytotoxic T-cells and natural killer cells. Excess ADORA2A activity has both a pro-excitotoxic and neuro-inflammatory effect in experimental models, providing substantial pre-clinical benefits for selective antagonists across brain diseases.

Fig.1 Impact of ADORA2A on the tumor-immune microenvironment. (OA Literature)Fig.1 Impact of adenosine on the tumor-immune microenvironment (A2AR = ADORA2A).1

ADORA2A Is A Versatile Purinergic Orchestrator

ADORA2A coordinates diverse physiological programs simultaneously, complicating its classical classification as an adenosine sensor:

  • Immune Checkpoint & Inflammation Resolver: In the tumor microenvironment and chronically inflamed tissues, ADORA2A activation on effector lymphocytes increases intracellular cAMP and engages PKA-related signaling, which suppresses proximal T-cell receptor signaling, cytokine production, and cytotoxic effector functions while promoting a more regulatory T-cell phenotype.
  • Neuroprotective Modulator: Heteromeric complexes of ADORA2A, dopamine D2 receptors and metabotropic glutamate receptor 5 in the basal ganglia are involved in striatal output modulation motor control.
  • Therapeutic Biologics Target: Small-molecule ADORA2A antagonists, identified in recent successes of adenosine receptor blockade strategies demonstrated through oncology studies have exponentially raised the bar for structurally unique recombinant receptors and reprogrammed bio-architechtonic validated cellular platforms further recapitulating feedback-inducible adenosinergic T Cell suppression with conformation-specific antibodies.

ADORA2A Membrane Protein Product

We develop a customized suite of ADORA2A membrane protein products to support structural, ligand-binding, biochemical, and functional studies of this purinergic GPCR. Because appropriate receptor folding and membrane-associated conformation are important for preserving ligand-binding and signaling-related properties, available preparations and construct formats are designed to meet different experimental requirements. These products may be suitable for studies of orthosteric and allosteric ligand interactions, receptor structure, pharmacological modulation, and related functional mechanisms. Appropriate quality assessment is applied according to the intended research use and specific product format.

ADORA2A Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

ADORA2A Stable Cell Line Product

Physiologically representative cellular platforms are critical for elucidating ADORA2A-mediated purinergic signaling and benchmarking therapeutic discovery pipelines. We provide to the scientific community High-quality ADORA2A stable cell lines that maintain true plasma membrane localization, native glycosylation signatures, and functional response patterns upon exposure to drugs, including adenosine. In addition to those of wild-type ADORA2A, our platforms include constitutively active mutants; naturally occurring coding variants associated with neuropsychiatric phenotypes; and polymorphisms that enhance or reduce G protein coupling efficiency. We next created reporter-coupled lines for mechanistic dissection of ADORA2A-driven biology, which include cAMP response element-driven luciferase as well as assays to measure β-arrestin recruitment and calcium mobilization in real time upon agonist stimulation or antibody blockade. We also provide co-expression systems to reconstitute heteromeric receptor complexes of ADORA2A with either the dopamine D2 receptor or adenosine A1 receptors in one cell background, allowing for studies on allosteric crosstalk without transgenically expressing a second subunit.

ADORA2A Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

ADORA2A Recombinant Antibody Product

We offer a range of sequence-defined recombinant antibodies against ADORA2A for diverse research applications. These reagents are designed to support the detection, localization, and analysis of ADORA2A in appropriate research samples and model systems. Depending on the specific product, ADORA2A antibodies may be suitable or available for selected applications such as Western Blotting, ELISA, Flow Cytometry, Immunofluorescence, and related antibody-based assays. Product-specific application suitability and performance should be determined based on the corresponding antibody data and experimental conditions.

ADORA2A Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Superior Batch-to-Batch Consistency: Stringent quality controls to ensure low variability from batch to batch.
  • Customization Options: Tags/Labels/package Modifications available upon request.

Custom ADORA2A Membrane Protein and Antibody Discovery Services

In addition to our catalog products, we offer a suite of comprehensive end-to-end protein design and engineering services for complex purinergic GPCRs such as ADORA2A:

  • Production & Validation: Cloning of the synthesized optimized gene into an expression vector, plus small-scale expression trials to help determine the best expression conditions.
  • Custom Antibody Production: Produced via large-scale expression in mammalian/insect/cell culture or bacterial expression systems, purified in detergent or reconstituted into nanodiscs.
  • Engineered Cell Lines: Creation of stable cell lines that physiologically mimic endogenous ADORA2A expression and activity.
  • Functional Assessment Systems: Designing and executing assays to assess protein function and ligand binding.

Frequently Asked Questions (FAQ)

  1. Do your ADORA2A products need to be co-expressed with G proteins for correct pharmacology?

    We produce ADORA2A membrane proteins in complex with heterotrimeric Gs protein for optimal coupling and ligand-binding kinetics. The receptor-G protein complex are available pre-assembled and can be supplied co-reconstituted with β-arrestin upon request.

  2. Do your ADORA2A products need specific post-translational modifications?

    Our products include the essentials for glycosylation and proper disulfide bond formation to maintain correct folding, membrane insertion and recognition by conformational dependent antibodies. Quality control explicitly approves these changes before release.

  3. Is there any way we can get ADORA2A without deletion of its domain as to know what could be the functional region?

    Specific deletions in the N-terminal extracellular domain, individual loops and/or C-terminus that contains serine phosphorylation sites. These have the advantage of allowing for large structure-function studies and creating dominant-negative mutants.

  4. Can your ADORA2A recombinant proteins be introduced into human subjects for therapeutic management of Parkinson's disease, sleep disorders, or inflammatory tissue damage?

    No—our ADORA2A products including recombinant proteins, stable cell lines and antibody reagents are only used for preclinical research purpose. None of them have passed the safety, sterility or regulatory hurdles requisite for use in human subjects.

Reference
  1. Shreenivas, Aditya, et al. "Clinical and biologic correlates of ADORA2A transcriptomic expression in cancer." International Journal of Molecular Sciences 25.9 (2024): 4742. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/ijms25094742
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