AZD 9272

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效、选择性、中枢神经系统高度渗透性、口服的 mGluR5 负变构调节剂，Kd 为 2.8 nM。

A potent, selective, highly CNS-penetrant and orally available mGluR5 negative allosteric modulator Kd of 2.8 nM; does not elicit any agonist, antagonist or positive allosteric modulator on any of the other seven mGluR subtypes at 30 uM; completely reverses the glutamate-stimulated phosphatidyl inositol hydrolysis in human mGluR5-GHEK cells with IC50 of 26 nM, causes psychoactive effects selectively mediated by mGluR5 mechanisms in vivo,Pain Phase 1 Discontinued.

AZD 9272 causes a concentration dependent decrease in the magnitude of the intracellular Ca2+ response to 1.5 μM of the mGluR group I selective agonist DHPG in both the human and the rat mGluR5 expressing cell lines. The maximal inhibition is 100%. The mean IC50 (±SD) value at the human mGluR5 is 7.6±1.1 nM (n=13) for AZD9272. The mean IC50 value at the rat mGluR5 is 2.6±0.3 nM (n=3) for AZD9272. In contrast, 10 μM of AZD9272 does not diminish the response to 10 μM ATP in the background GHEK cells. Increasing concentrations of AZD9272 causes a decrease in the potency and the maximal response of DHPG. AZD9272 completely reverses the glutamate-stimulated (EC80, 80 μM) phosphatidyl inositol hydrolysis in human mGluR5-GHEK cells in a concentration-dependent manner, with IC50 of 26±3 nM (n=21).

The clearance of AZD 9272 is low following a single intravenous dose at 3 μmol/kg and AZD 9272 is eliminated from plasma with terminal half-lives between 2 and 6 h. The terminal half-lives following oral dosing are similar to the half-lives following intravenous dosing. The volume of distribution at steady state is intermediate for AZD9272. AZD9272 causes no cocaine-appropriate responding and causes a non-dose-dependent reduction in response rates at higher doses. AZD9272 at 2.84 mg/kg causes greater than 80% and typically more than 99% MTEP-appropriate responding up to 20 hours after dose, with a decline to approximately 20% at 24 hours after dose, yielding a t1/2 of 21.93 hours, and causes no systematic effects on response rates. The first time point at which AZD9272 causes >90% MTEP-appropriate responding is at 30 minutes after dose.

AZD9272 | AZD-9272

GPCR/G Protein

mGluR

mGluR

Neurological Disease

Pain

327056-26-8

284.226

C14H6F2N4O

>98% (HPLC)

——

N#CC1=CC(C2=NC(C3=NC=C(F)C=C3)=NO2)=CC(F)=C1

3-fluoro-5-(3-(5-fluoropyridin-2-yl)-1,2,4-oxadiazol-5-yl)benzonitrile

(-20℃)

With Ice Pack

≥ 2 years