Adenosine receptors (AR) include a group of G protein coupled receptors (GPCRs) that mediate the physiological effects of adenosine. Meanwhile, AR has four subtypes, namely A1, A2A, A2B, and A3, each with unique pharmacological characteristics, tissue distribution, and effector coupling. Nonetheless, these four subtypes are all members of the GPCR superfamily and are most closely related to biogenic amine receptors. Importantly, GPCR is an important component of the whole body signaling network. Particularly, A2AR is expressed in various immune cells such as regulatory T cells, cytotoxic T cells, and macrophages. Obviously, adenosine binding to A2AR receptors can activate typical G proteins, triggering the cAMP/PKA/CREB pathway. The adenosine A2AR pathway plays an important role in protecting normal organs and tissues from immune cell autoimmune reactions. Here, we will introduce an adenosine A2A receptor antagonist for neurological disease research, SCH 58261.

SCH 58261 is an Adenosine Receptor A2A Antagonist for Neurological Disease Research.

At first, SCH 58261 is a potent, selective and competitive antagonist of adenosine A2A receptor with an IC50 of 15 nM. Besides, SCH 58261 displays 323-, 53- and 100-fold more selective for A2A receptor than A1, A2B, and A3 receptors, respectively.

Secondly, SCH 58261 decreases cell viability in a concentration-dependent in the NSCLC cell line H1975. Moreover, SCH58261 (25 μM; 72 hours) can inhibit the growth of CAF cells.

Thirdly, SCH 58261 causes a decrease in the tumor burden in a NSCLC mouse model. Furthermore, SCH 58261 partially decreases the haloperidol-induced catalepsy. the increase in the PENK mRNA expression in both dorsolateral and ventrolateral parts of the striatum at all three examined levels. Additionally, SCH 58261 diminishes the parkinsonian-like muscle rigidity and potentiates the effect of L-DOPA in rat model.

Finally, SCH 58261 is an adenosine A2A receptor antagonist for neurological disease research.


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