ADX47273

ADX-47273 is a potent and selective mGluR5 receptor PAM (positive allosteric modulator), EC50 = 0.17 μm, with no effect on other mGluR subtypes. In vivo, ADX47273 increased extracellular signal-regulated kinase and cAMP-responsive element-binding protein phosphorylation in hippocampus and prefrontal cortex, both of which are critical for glutamate-mediated signal transduction mechanisms. The mGluR (metabotropic glutamate receptor) is a group of G-protein coupled receptors and is active through an indirect metabotropic process. It plays a critical role in regulating synaptic plasticity and neural network activity.

Product information

CAS Number: 851881-60-2

Molecular Weight: 369.36

Formula: C20H17F2N3O2

Chemical Name: (S)-(4-fluorophenyl)(3-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)methanone

Smiles: O=C(C1C=CC(F)=CC=1)N1C[C@H](CCC1)C1=NC(=NO1)C1C=CC(F)=CC=1

InChiKey: VXQCCZHCFBHTTD-HNNXBMFYSA-N

InChi: InChI=1S/C20H17F2N3O2/c21-16-7-3-13(4-8-16)18-23-19(27-24-18)15-2-1-11-25(12-15)20(26)14-5-9-17(22)10-6-14/h3-10,15H,1-2,11-12H2/t15-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: ≥ 31 mg/mL

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

ADX-47273 increased (9-fold) the response to threshold concentration of glutamate (50 nM) in fluorometric Ca(2+) assays (EC(50) = 170 nM) in human embryonic kidney 293 cells expressing rat mGlu5. ADX47273 dose-dependently shifted mGlu5 receptor glutamate response curve to the left (9-fold at 1 microM) and competed for binding of [(3)H]2-methyl-6-(phenylethynyl)pyridine (K(i) = 4.3 microM), but not [(3)H]quisqualate.

In Vivo:

ADX47273 increased extracellular signal-regulated kinase and cAMP-responsive element-binding protein phosphorylation in hippocampus and prefrontal cortex, both of which are critical for glutamate-mediated signal transduction mechanisms. In models sensitive to antipsychotic drug treatment, ADX47273 reduced rat-conditioned avoidance responding [minimal effective dose (MED) = 30 mg/kg i.p.] and decreased mouse apomorphine-induced climbing (MED = 100 mg/kg i.p.), with little effect on stereotypy or catalepsy. ADX47273 had no effect on single-session and multi-session extinction, but administration of ADX47273 after a single retrieval trial enhanced subsequent fear extinction learning .

References:

1. Liu F, et al. ADX47273 [S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]-oxadiazol-5-yl]-piperidin-1-yl}-methanone]: a novel metabotropic glutamate receptor 5-selective positive allosteric modulator with preclinical antipsychotic-like and procognitive.
2. Xu J, et al. Potentiating mGluR5 function with a positive allosteric modulator enhances adaptive learning. Learn Mem. 2013 Jul 18;20(8):438-45.

Products are for research use only. Not for human use.