| Description | VU0422288 (ML396) is a potent orthosteric modulator of type III mGlu receptors (mGlus).VU0422288 shows inhibition of mGluR4, mGluR7, and mGluR8 in a calcium mobilization assay.VU0422288 can be used to study Rett syndrome (RTT). |
| In vitro | 在含有海马体的冠状切片中，VU0422288 (1 μM；5分钟)增强了由30 μM LSP4-2022[1]引起的场兴奋性突触后电位（fEPSPs）斜率的下降。然而，单独使用VU0422288（浓度为1 μM，持续10分钟）时，并不改变fEPSP的斜率，这表明在刺激条件下，mGlu7在Mecp2-/y切片中不具备增强作用[1]。 |
| In vivo | 在Mecp2+/-小鼠中，VU0422288（30 mg/kg；腹腔注射；每天一次，连续17天）能够挽救突触可塑性缺陷和学习记忆表型，减少呼吸暂停的频率，而在Mecp2+/+动物中无效[1]。成年雄性斯普拉格-道利大鼠单次腹腔注射VU0422288（10 mg/kg）后，显示出血浆/大脑分配系数为1.67，预测脑内自由浓度约为40 nM[1]。 |
| Target activity | mGluR8:128 nM (EC50), mGluR7:146 nM (EC50), mGluR4:108 nM (EC50) |
| Synonyms | VU-0422288, ML-396, ML396, VU 0422288, ML 396 |
| molecular weight | 360.19 |
| Molecular formula | C17H11Cl2N3O2 |
| CAS | 1630936-95-6 |
| Storage | |Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 3.6 mg/mL (10 mM), Sonication is recommended. |
| References | 1. 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. 2. 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. |