VU0422288_product_DataBase

Bioactivity

VU0422288 (ML396) is a positive allosteric modulator of group III mGluRs. VU0422288 inhibits mGluRs with EC50s of 125 nM, 146 nM, and 108 nM for mGluR4, mGluR7, and mGluR8, respectively in calcium mobilization assays. VU0422288 reverses deficits in contextual fear memory, social recognition, and apneas in Rett syndrome (RTT) model mice[1][2].

Invitro

Vu0422288 (1 μM; 5 分钟) 在包含海马的冠状切片上，对 30 μM LSP4-2022 诱导的场兴奋性突触后电位 (fEPSPs) 斜坡减少有增强作用[1]。VU0422288 (1 μM; 10 分钟) 不能单独改变 fEPSP 的斜率，说明在刺激条件下，mGlu7 在 Mecp2-/y 切片中不具有补强活性[2]。

In Vivo

VU0422288 (30 mg/kg; 腹腔注射; 每天 1 次，共 17 天) 在 Mecp2+/- 小鼠中，可以挽救突触可塑性缺陷和学习记忆表型，减少了呼吸暂停频数，而在 Mecp2+/+ 动物中，则不起作用[2]。VU0422288 (10 mg/kg; 腹腔注射; 单剂量) 在成年雄性 Sprague-Dawley 大鼠的血浆/大脑划分系数为 1.67，预测游离脑浓度约为 40 nM[2]。

Name

VU0422288

CAS

1630936-95-6

Formula

C17H11Cl2N3O2

Molar Mass

360.19

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Jalan-Sakrikar N, et al. Identification of positive allosteric modulators VU0155094 (ML397) and VU0422288 (ML396) reveals new insights into the biology of metabotropic glutamate receptor 7. ACS Chem Neurosci. 2014 Dec 17;5(12):1221-37. [2]. Gogliotti RG, et al. mGlu7 potentiation rescues cognitive, social, and respiratory phenotypes in a mouse model of Rett syndrome. Sci Transl Med. 2017 Aug 16;9(403):eaai7459.

PeptideDB

VU0422288

CAS: 1630936-95-6 F: C17H11Cl2N3O2 W: 360.19