title: The A3 adenosine receptor as multifaceted therapeutic target: pharmacology, medicinal chemistry, and in silico approaches.
abstract: Adenosine is an ubiquitous local modulator that regulates various physiological and pathological functions by stimulating four membrane receptors, namely A(1), A(2A), A(2B), and A(3). Among these G protein-coupled receptors, the A(3) subtype is found mainly in the lung, liver, heart, eyes, and brain in our body. It has been associated with cerebroprotection and cardioprotection, as well as modulation of cellular growth upon its selective activation. On the other hand, its inhibition by selective antagonists has been reported to be potentially useful in the treatment of pathological conditions including glaucoma, inflammatory diseases, and cancer. In this review, we focused on the pharmacology and the therapeutic implications of the human (h)A(3) adenosine receptor (AR), together with an overview on the progress of hA(3) AR agonists, antagonists, allosteric modulators, and radioligands, as well as on the recent advances pertaining to the computational approaches (e.g., quantitative structure-activity relationships, homology modeling, molecular docking, and molecular dynamics simulations) applied to the modeling of hA(3) AR and drug design.
authors.affiliation: Department of Pharmacy, National University of Singapore, 3 Science Drive 2, Singapore 117543, Singapore.
authors.forename: Siew Lee
authors.initials: SL
authors.lastname: Cheong
authors.forename: Stephanie
authors.initials: S
authors.lastname: Federico
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Venkatesan
authors.forename: Alexander Laurence
authors.initials: AL
authors.lastname: Mandel
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Shao
authors.forename: Stefano
authors.initials: S
authors.lastname: Moro
authors.forename: Giampiero
authors.initials: G
authors.lastname: Spalluto
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pastorin
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000175:diagnosis / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000188:drug therapy; D058990:Molecular Targeted Therapy / Q000379:methods*; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology*; D043684:Receptor, Adenosine A3 / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
chemical_list: D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3