For research use only. Not for therapeutic Use.
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].
VU0422288 (1 μM; 5 min) enhances 30 μM LSP4-2022-induced reductions in the field excitatory postsynaptic potentials (fEPSPs) slope on Coronal slices containing the hippocampus[1].
VU0422288 (1 μM; 10 min) can not alter the fEPSP slopes alone, indicating that mGlu7 is not tonically active in Mecp2-/y slices under stimulation conditions[2].
VU0422288 (30 mg/kg; i.p.; once daily for 17 days) rescues synaptic plasticity defects and learning and memory phenotypes, reduces the number of apneas in Mecp2+/- mice, while VU0422288 has no effect in Mecp2+/+ animals[2].
VU0422288 (10 mg/kg; i.p.; single dose) exhibis a plasma/brain partitioning coefficient of 1.67 in adult male Sprague-Dawley rats, with predicted unbound brain concentration of about 40 nM[2].
| Catalog Number | I011180 |
| CAS Number | 1630936-95-6 |
| Synonyms | N-[3-chloro-4-(5-chloropyridin-2-yl)oxyphenyl]pyridine-2-carboxamide |
| Molecular Formula | C17H11Cl2N3O2 |
| Purity | ≥95% |
| InChI | InChI=1S/C17H11Cl2N3O2/c18-11-4-7-16(21-10-11)24-15-6-5-12(9-13(15)19)22-17(23)14-3-1-2-8-20-14/h1-10H,(H,22,23) |
| InChIKey | MZRLPXFGQKQHST-UHFFFAOYSA-N |
| SMILES | C1=CC=NC(=C1)C(=O)NC2=CC(=C(C=C2)OC3=NC=C(C=C3)Cl)Cl |
| 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. |
