MS48107 是一种有效的 G 蛋白偶联受体 68 (GPR68) 的选择性正变构调节剂。MS48107 对 GPR68 的选择性高于密切相关的质子 GPCR，神经递质转运蛋白和 hERG 离子通道。MS48107 可以轻松穿越小鼠的血脑屏障 (BBB)。
MS48107 is a potent and selective positive allosteric modulator of G protein-coupled receptor 68 (GPR68). MS48107 is selective for GPR68 over the closely related proton GPCRs, neurotransmitter transporters, and hERG ion channels. MS48107 can readily cross the blood-brain barrier (BBB) in mice[1].
5-HT2B has moderate binding affinity to MS48107 (compound 71) with a Ki value of 219 nM. At 5-HT2B receptors, MS48107 shows no agonist activity but display weak antagonist activity with a Ki value of 310 nM, respectively[1].MS48107 (compound 71) has agonist activity only at the MT1 and MT2 receptors. MS48107 is a weak full agonist at the MT1 receptor (EC50 = 320 nM) and a weak partial agonist activity at the MT2 receptor (EC50 = 540 nM). MS48107 displays low binding affinities to MT1 (5900 nM) and MT2 (1100 nM) receptors[1].
For MS48107 (compound 71), a single intraperitoneal injection at the dose of 25 mg/kg leads to high exposure levels (above 10 μM) in both plasma and brain at 0.5 h in mice (Swiss Albino mice). The high compound exposure levels in both plasma and brain are maintained for 2 h[1].
[1]. Xufen Yu, et al. Design, Synthesis, and Characterization of Ogerin-Based Positive Allosteric Modulators for G Protein-Coupled Receptor 68 (GPR68). J Med Chem. 2019 Aug 22;62(16):7557-7574.
动态评分
0.0