Irreversible Antagonists for the Adenosine A_2B Receptor.

ABSTRACT: Blockade of the adenosine A_2B receptor (A_2BAR) represents a potential novel strategy for the immunotherapy of cancer. In the present study, we designed, synthesized, and characterized irreversible A_2BAR antagonists based on an 8-p-sulfophenylxanthine scaffold. Irreversible binding was confirmed in radioligand binding and bioluminescence resonance energy transfer(BRET)-based Gα₁₅ protein activation assays by performing ligand wash-out and kinetic experiments. p-(1-Propylxanthin-8-yl)benzene sulfonyl fluoride (6a, PSB-21500) was the most potent and selective irreversible A_2BAR antagonist of the present series with an apparent K_i value of 10.6 nM at the human A_2BAR and >38-fold selectivity ver

SUBMITTER: Temirak A 

PROVIDER: S-EPMC9231011 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature