1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECR4056Cat. No.: HY-100179CAS No.: 1004997-71-0分式: CHN分量: 272.3作靶點: Monoamine Oxidase; Imidazoline Receptor作通路: Neuronal Signaling; GPCR/G Protein儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMS

2、O : 30 mg/mL (110.17 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 3.6724 mL 18.3621 mL 36.7242 mL5 mM 0.7345 mL 3.6724 mL 7.3448 mL10 mM 0.3672 mL 1.8362 mL 3.6724 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 CR4056個選擇性的重 組 MAO-A 抑制劑，其 IC50 值為 202.7

3、nM。 CR4056 也是咪唑啉-2 受體 (I2R) 的配體，其 IC50 值為 596 nM。IC50 & Target IC50: 202.7 nM (MAO-A), 596 nM (I2R) 1體外研究CR4056 is an imidazoline-2 receptor (I2R) ligand with an IC50 of 59676 nM. CR4056 is also an inhibitor ofboth human recombinant MAO-A and MAO-B with IC50s of 202.710.3 and 10000, respectively 1.

4、The co-1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEtreatment of bortezomib (BTZ) with CR4056 at all the concentrations used (range 3 to 30 M) does notinduce any significant difference in cell survival compare with BTZ-treated cells, either in H929 or in RPMI8226 myeloma cells 2.體內(nèi)研究 Two hours a

5、fter a single oral dose of 20 mg/kg CR4056, endogenous norepinephrine (NE) levels increase by68.2%14.1% (P50=5.8 mg/kg) (P 1.PROTOCOLKinase Assay 1 Binding assays on monoamine oxidases in rat cerebral cortical membranes are conducted. In summary, forthe MAO-A binding assay, tritiated N-(2-aminoethyl

6、)-5-(m-fluorophenyl)-4-thiazole carboxamide HCl (3HRo41-1049, 10 nM) is incubated in the absence or presence of CR4056 for 60 minutes at 37C and non specificbinding is determined in the presence of 1 M clorgyline. For the MAO-B binding assay, incubation of 3HRo19-6327(tritiated lazabemide) (15 nM) i

7、s carried out for 90 minutes at 22C and non specific binding isdetermined in the presence of 10 M (R)-deprenyl 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 To rule out any interference of CR4056 with bortezomib (BTZ)-induced cytotoxici

8、ty, non-small cell lungcancer and MM cell lines are simultaneously treated for 72 hours with BTZ and CR4056. Cells are exposedto the IC50 of BTZ, estimated in the cytotoxicity study, with or without three concentrations of CR4056 (3, 10,and 30 M). The incubations with CR4056 alone (3, 10, and 30 M)

9、and with the highest dose of vehicle(DMSO) are also performed. Growth inhibition is assessed by MTT assay. In these experiments, the CR4056is tested in vitro in a range of concentrations spanning from pharmacological to toxicological levels 2.MCE has not independently confirmed the accuracy of these

10、 methods. They are for reference only.Animal Rats: Rats are fasted overnight before drug administration. A first measurement of pain threshold isAdministration 1 undertaken before capsaicin injection. Capsaicin is administered at time t=0 by the intraplantar route in theright hind paw (10 L of a 1 m

11、g/mL Tween 80/saline solution). Sixty minutes later, animals are dosed by theoral route with CR4056 (3 to 30 mg/kg) or its vehicle in a volume of 5 mL/kg. A sham control group is alwayspresent for comparison. In mechanistic studies, antagonists are administered 30 minutes after capsaicin and15 minut

12、es before CR4056 administration 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Ferrari F, et al. Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain.J Pain Res. 2011;4:111-25.2. Meregalli C, et al. CR4056, a new analgesic I2 ligand, is highly effective against bortezomib-induced painful neuropathy in rats. J PainRes. 2012;5:151-67.McePdfHeightCa