sch-202676 and Astrocytoma

The G protein-coupled receptor allosteric modulator SCH-202676 (N-(2,3-diphenyl-1,2,4-thiadiazol-5-(2H)-ylidene)methanamine), which affects a wide range of structurally unrelated G protein-coupled receptors, has highly divergent effects on purine receptors. SCH-202676 inhibited radioligand binding to human adenosine A(1), A(2A), and A(3) receptors (IC(50) = 0.5-0.8 microM) and affected dissociation kinetics, but at the human P2Y(1) nucleotide receptor it had no effect. SCH-202676 (10 microM) selectively accelerated agonist dissociation at adenosine A(3) receptors and either slowed (adenosine A(1) receptors) or accelerated (adenosine A(2A) receptors) antagonist dissociation. Thus, SCH-202676 differentially modulated A(1), A(2A), and A(3) receptors as well as agonist- and antagonist-occupied receptors.

Topics: Allosteric Regulation; Animals; Astrocytoma; Binding, Competitive; Brain Neoplasms; Cells, Cultured; CHO Cells; Cricetinae; Humans; Kidney; Kinetics; Radioligand Assay; Rats; Receptor, Adenosine A1; Receptor, Adenosine A2A; Receptor, Adenosine A3; Receptors, Purinergic P2; Receptors, Purinergic P2Y1; Thiadiazoles; Thiazoles