A2Aselektiv

A2A selectivity refers to the preference of a chemical compound to bind to the adenosine A2A receptor over other adenosine receptor subtypes (A1, A2B, A3). This selectivity is typically quantified using binding or functional assays that report Ki or EC50 values, and by selectivity ratios such as Ki(A2A) divided by Ki at the other receptor types. A compound is considered A2A-selective when these ratios indicate markedly higher potency or affinity for A2A, often by more than 100-fold in comparison with the other subtypes.

Receptors and signaling: The A2A receptor is a Gs-coupled receptor whose activation stimulates adenylate cyclase and increases intracellular cAMP. It is particularly abundant in the striatum and exhibits functional interactions with dopamine D2 receptors, a relationship that underpins some of its relevance to motor control and neurodegenerative disease.

Applications: A2A-selective antagonists are studied for therapeutic use in Parkinson’s disease, where they can complement dopaminergic therapy and may reduce L-dopa-induced dyskinesias. Notable examples include istradefylline (KW-6002), an A2A antagonist used clinically in some regions, as well as research tools such as SCH58261 and ZM241385. In oncology, A2A antagonists are explored for cancer immunotherapy, aiming to relieve adenosine-mediated immunosuppression and enhance anti-tumor T cell responses. The field includes a range of clinical trials and preclinical studies exploring different indications.

Chemistry and selectivity: A2A ligands are often purine- or xanthine-derived compounds. Potency is reported as Ki or EC50, with high-quality A2A antagonists typically showing subnanomolar Ki values and substantial selectivity over A1, A2B, and A3 receptors. The exact profile depends on the specific compound and assay context.