A-967079 - TRP Channel Antagonist - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEA-967079Cat. No.: HY-108463CAS No.: 1170613-55-4分式: CHFNO分量: 207.24作靶点: TRP Channel作通路: Membrane Transporter/Ion Channel; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMS : 10

2、0 mg/mL (482.53 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (12.06 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (12.06 mM); Clear solution1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 A-967079种选择性 TRPA1 受体拮

3、抗剂，对和 TRPA1 受体的 IC50 分别为 67 nM 和 289 nM，并且具有良好的 CNS 穿透性。IC50 & Target IC50: 67 nM (human TRPA1 receptor), 289 nM (rat TRPA1 receptor) 1体内研究 Systemic injection of A-967079 (30 mol/kg, i.v.) decreases the responses of wide dynamic range (WDR),and nociceptive specific (NS) neurons following noxious pin

4、ch stimulation of the ipsilateral hind paw inuninjured and CFA-inflamed rats. Similar to its actions in uninjured rats, administration of A-967079 (30 mol/kg, i.v.) to complete Freunds adjuvant (CFA)-inflamed rats significantly reduces WDR neuronalresponses to noxious pinch stimulation compared to b

5、aseline firing (p=0.0013, repeated-measures ANOVA)and the vehicle group (p=0.0001, two-way ANOVA). The maximum observed effect (61.110.97% decreasefrom baseline levels) on pinch-evoked activity in inflamed rats occur 35 min after injection. In contrast touninjured rats, injection of A-967079 to CFA-

6、inflamed rats also significantly (p=0.0004, and p=0.0001 for therepeated-measures and two-way ANOVAs, respectively) reduces responses of WDR neurons to 10-g vonFrey hair stimulation. The maximal observed decrease in von Frey-evoked activity is 67.6918.39% frombaseline levels (35 min post-injection),

7、 and is thus comparable to the effects of A-967079 on pinch-evokedactivity in inflamed rats 1.PROTOCOLAnimal Rats 1Administration 1 Male Sprague-Dawley rats (250-400 g) are used for all experiments and are housed in a temperaturecontrolled room with a 12/12-hr day/night cycle. Food and water are ava

8、ilable ad libitum. Spontaneous andevoked neuronal activity is then measured 5, 15, 25, and 35 min after systemic injection of A-967079 (30 mol/kg, i.v.) or vehicle (polyethylene glycol). The intravenous injection of A-967079 or vehicle is completedover a 6-7 min period. The i.v. dose of A-967079 is

9、selected based on extrapolated plasma levels that areeffective in behavioral studies 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. McGaraughty S, et al. TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic,and inflamed rats. Mol Pain. 2010 Mar 5;6:14.McePdfHeightCaution: Product has not been fully validated for m