GPR149 Inhibitors

Chemical inhibitors of GPR149 can function through various mechanisms that involve interference with the Gq protein signaling pathway, which is integral to the activity of GPR149 as a G protein-coupled receptor. BPTU operates as a selective allosteric antagonist of the P2Y1 receptor, and by impeding P2Y1, it can downregulate the Gq protein-mediated signaling pathways, potentially diminishing GPR149 activity. Likewise, suramin, as a non-selective antagonist of P2 purinergic receptors, can disrupt ATP-mediated G protein-coupled receptor signaling, thus indirectly decreasing GPR149 activity by attenuating overall purinergic signaling within the cell. Another chemical, YM-254890, offers a more targeted approach by selectively inhibiting Gq/11 protein signaling, which can lead to an indirect inhibition of GPR149, presuming GPR149 signals through the same pathway. Furthermore, UBO-QIC, which serves as an inverse agonist for GPR17, can indirectly inhibit GPR149 by reducing the availability of active Gq/11 proteins, while ML-109 antagonizes GPR35, thereby potentially decreasing GPR149 activity by limiting Gq protein-mediated signal transduction. L-161,982 and AH 6809, as antagonists of the EP4 receptor and both EP2 and EP4 prostaglandin receptors respectively, can impede the signaling of Gq proteins and in turn, decrease GPR149's functional activity. Similarly, MRS 2500 and MRS 2179, by antagonizing the P2Y1 receptor, can diminish Gq protein signaling, which may reduce GPR149 activity. CID 16020046, an antagonist of the CysLT1 receptor, SCH-202676, a broad-spectrum GPCR antagonist, and ONO-AE3-208, another EP4 receptor antagonist, all function by inhibiting receptors that utilize Gq proteins for signaling, thereby reducing the functional signaling capacity of GPR149.