LY3020371 hydrochloride

LY3020371 hydrochloride用途

LY3020371 hydrochloride 是一种有效的选择性代谢型谷氨酸 2/3 受体 (mGlu2/3) 拮抗剂,Ki 值分别为 5.3 nM 和 2.5 nM。LY3020371 hydrochloride 有效阻断 cAMP 形成,IC50 值为 16.2 nM。LY3020371 hydrochloride 在体内具有抗抑郁样特性。

LY3020371 hydrochloride名称

[ CAS 号 ]:
1377615-44-5

[ 英文名 ]:
LY3020371 hydrochloride

LY3020371 hydrochloride生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 谷氨酸受体

研究领域 >> 神经疾病

[ 靶点 ]

mGluR2:5.3 nM (Ki)

mGluR3:2.5 nM (Ki)

[体外研究]

LY3020371盐酸盐(LY3020371.HCl)以高亲和力(hmGlu2 Ki = 5.26 nM; hmGlu3 Ki = 2.50 nM)取代mGlu2/3激动剂配体[3H]-459477的结合[1]。LY3020371盐酸盐(LY3020371.HCl)(0.1nM-100μM; 1小时)有效阻断mGlu2/3激动剂(DCG-IV)抑制的,福司柯林刺激的cAMP形成(IC50 = 16.2nM),这种效应在表达hmGlu3的细胞中也观察到(IC50 = 6.21nM)[1]。LY3020371盐酸盐(LY3020371.HCl)阻断激动剂抑制的自发Ca2+振荡(IC50 = 34 nM)和完整的海马切片制备(IC50 = 46 nM)[1]。

[体内研究]

LY3020371盐酸盐(LY3020371.HCl)(静脉注射；3-15 mg/kg)导致脑脊液药物水平,预期可有效阻断mGlu2/3受体[1]。LY3020371盐酸盐(LY3020371)(腹膜内注射；3mg/kg,10_mg/kg；2小时)具有明显的促醒作用,导致Wistar大鼠在轻度阶段的NREM睡眠大大减少[3]。

[参考文献]

[1]. Witkin JM, et al. In vitro pharmacological and rat pharmacokinetic characterization of LY3020371, a potent and selective mGlu2/3 receptor antagonist. Neuropharmacology. 2017 Mar 15;115:100-114.

[2]. Witkin JM, et al. Preclinical predictors that the orthosteric mGlu2/3 receptor antagonist LY3020371 will not engender ketamine-associated neurotoxic, motor, cognitive, subjective, or abuse-liability-related effects. Pharmacol Biochem Behav. 2017 Apr;155:43-55.

[3]. Wood CM, et al. Investigating the role of mGluR2 versus mGluR3 in antipsychotic-like effects, sleep-wake architecture and network oscillatory activity using novel Han Wistar rats lacking mGluR2 expression. Neuropharmacology. 2018 Sep 15;140:246-259.

LY3020371 hydrochloride物理化学性质

[ 分子式 ]:
C₁₅H₁₆ClF₂NO₅S

[ 分子量 ]:
395.81

LY3020371 hydrochloride

LY3020371 hydrochloride用途

LY3020371 hydrochloride名称

LY3020371 hydrochloride生物活性

LY3020371 hydrochloride物理化学性质

推荐生产厂家/供应商：

相关化合物