Neu2000 _iGluR Antagonist - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENeu2000Cat. No.: HY-106408CAS No.: 640290-67-1分式: CHFNO分量: 383.22作靶點(diǎn): iGluR作通路: Membrane Transporter/Ion Channel; Neuronal Signaling儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 112.5 mg/

2、mL (293.57 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.6095 mL 13.0473 mL 26.0947 mL5 mM 0.5219 mL 2.6095 mL 5.2189 mL10 mM 0.2609 mL 1.3047 mL 2.6095 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Neu2000種競(jìng)爭(zhēng)性的 N-甲基-D-天冬氨酸 (NM

3、DA) 受體拮抗劑。IC50 & Target NMDA receptor 1體外研究Neu2000 shows apparent neuroprotection against 300 M N-methyl-D-aspartate (NMDA) at doses as low as30 M. Neu2000 does not protect cortical neurons against -amino-3-hydroxy-5-methyl-4-isoxazolepropionic1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEacid- o

4、r kainate-mediates excitotoxicity. Neu2000 inhibits the electrophysiologic response of cultured corticalneurons to 300 M NMDA in a concentration-dependent manner, indicating that the effect is mediated by aspecific action at NMDA receptors. The Neu2000 dose-response has an IC50 of 35.385.94 M and Hi

5、llscoefficient of 0.91 (n=8). Neu2000 (100 M) significantly reduces the maximal NMDA response by58.312.72% (n=5) and the EC50 values of NMDA from 18.881.85 to 9.920.17 M (n=5, P 1.體內(nèi)研究 Pharmacokinetic analysis reveals that the half-life of Neu2000 is 1.42, 2.14, and 1.79h followingintraperitoneal ad

6、ministration of 10, 25, and 50mg/kg, respectively. In addition, the Cmax (maximum plasmaconcentration) is calculated as 3.86, 18.73, and 52.83g/mL and the AUC (area under the curve) isdetermined to be 7.37, 55.15, and 96.77g/h/mL at the same respective doses. The levels of basalmitochondrial ROS are

7、 significantly elevated at 24h post-surgery in both the vehicle-treated (4.1-fold, p 2.PROTOCOLCell Assay 1 Whole-cell voltage-clamp recordings are performed on primary cultured cortical neurons (11 to 14 DIV) atroom temperature (18C to 23C). Whole-cell currents are recorded and analyzed using an am

8、plifier. The 2to 3-M-resistance recording pipettes are filled with an internal solution containing 135 mM CsCl, 10 mM N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid, 1.2 mM MgCl2, 4 mM ATP-Na2, 0.5 mM CaCl2, and 11mM ethyleneglycol tetraacetate (pH adjusted to 7.3 with CsOH). The external soluti

9、on is composed of 140mM NaCl, 2 mM KCl, 2 mM CaCl2, 10 mM N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid, and 0.01mM glycine (pH adjusted to 7.3 to 7.4 with NaOH). N-methyl-D-aspartate and Neu2000 solutions areprepared by dissolving these chemicals in the external solutions, and they are applied

10、 to target neuronsusing a gravity-driven superfusion system with a linear array of 8 to 10 barrels. Graphing of data and dose-response analysis are performed and all data are presented as means.e 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal

11、The pharmacokinetic profile of Neu2000 in normal rats is examined using intraperitoneal (ip) route ofAdministration 2 administration. Rats are anesthetized by ether inhalation and the femoral artery cannulated. Rats are placedinto cages for 1h and then receive injections (10, 25, or 50mg/kg ip, n=6

12、per dose) of Neu2000 dissolved insterile saline. Blood is collected from the femoral artery at 15, 30, 60, 120, 240, 480, and 1440min followinginjection. Plasma aliquots of 50L are spiked with 100L of internal standard solution (Neu2000IS, 10g/mLin acetonitrile). After vortex mixing for 1min, the sa

13、mples are centrifuged at 12,000g for 5min. A total of 50L of the supernatant phase is separated and diluted with 50L of distilled water. Plasma concentrationsrelative to time are obtained using liquid chromatography-mass spectrometry 2.MCE has not independently confirmed the accuracy of these method

14、s. They are for reference only.REFERENCES1. Gwag BJ, et al. Marked prevention of ischemic brain injury by Neu2000, an NMDA antagonist and antioxidant derived from aspirin andsulfasalazine. J Cereb Blood Flow Metab. 2007 Jun;27(6):1142-51.2. Springer JE, et al. The functional and neuroprotective actions of Neu2000, a dual-acting pharmacological agent, in the treatment ofacute spinal cord injury. J Neurotrauma. 2010 Jan;27(1):139-49.McePdfHeight2/2 Master of Small