ADX-47273|ADX47273|PAMs|DC Chemicals

ADX-47273|ADX47273|PAMs|DC Chemicals
ADX-47273 is a novel, potent and selective metabotropic glutamate receptor 5 allosteric modulator with an EC50 of 170 nM.

Catlog: DC8087| Product name: ADX 47273| Cas: 851881-60-2| Other names: ADX-47273,ADX47273| Molecule Formula: C20H17F2N3O2| MW: 369.36. Purity: >98%

Price: 100mg: 650 USD; 250mg: 1000 USD; 1000mg: 1900 USD

ADX-47273 is a novel, potent and selective metabotropic glutamate receptor 5 allosteric modulator with an EC50 of 170 nM. ADX-47273 shifted mGlu5 receptor glutamate response curve to the left. ADX-47273 elevated extracellular signal-regulated kinase and cAMP-responsive element-binding protein phosphorylation in hippocampus and prefrontal cortex.ADX47273 [S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-methanone], a recently identified potent and selective mGlu5 PAM, 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. In the same system, 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. Furthermore, ADX47273 blocked phencyclidine, apomorphine, and amphetamine-induced locomotor activities (MED = 100 mg/kg i.p.) in mice and decreased extracellular levels of dopamine in the nucleus accumbens, but not in the striatum, in rats. In cognition models, ADX47273 increased novel object recognition (MED = 1 mg/kg i.p.) and reduced impulsivity in the five-choice serial reaction time test (MED = 10 mg/kg i.p.) in rats. Taken together, these effects are consistent with the hypothesis that allosteric potentiation of mGlu5 may provide a novel approach for development of antipsychotic and procognitive agents.

For research and scientific purpose only, not for human use.