Rotigotine-N-0437-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERotigotineCat. No.: HY-75502CAS No.: 99755-59-6Synonyms: N-0437; N-0923分式: CHNOS分量: 315.47作靶點: Dopamine Receptor; Adrenergic Receptor; 5-HT Receptor作通路: GPCR/G Protein; Neuronal Signaling儲存式: Powder -20C 3 years4C 2 yearsIn solv

2、ent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 50 mg/mL (158.49 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 3.1699 mL 15.8494 mL 31.6987 mL5 mM 0.6340 mL 3.1699 mL 6.3397 mL10 mM 0.3170 mL 1.5849 mL 3.1699 mL請根據產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

3、。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案，配制前請先配制澄清的儲備液，再依次添加助溶劑(為保證實驗結果的可靠性，體內實驗的作液，建議您現現配，當天使；澄清的儲備液可以根據儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 3.5 mg/mL (11.09 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 3.5 mg/

4、mL (11.09 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 3.5 mg/mL (11.09 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Rotigotine是dopamine receptor 純激動劑，是5-HT1A receptor 的部分激動劑，以及 2B-adrenergicreceptor 的拮抗劑，Ki 值分別為 0.71 nM (dopamine D3

5、 receptor)，4-15 nM (D2，D5，D4 receptors)，83nM (dopamine D1 receptor)。IC50 & Target Ki: 0.71nM (dopamine D3 receptor), 4-15nM (D2, D5, D4 receptors), 83nM (dopamine D1 receptor) 1 2,176 nM (1A), 273 nM (1B), 338 nM (2A), 27 nM (2B), 30 nM (5-HT1A), 86 nM (5-HT7) 2體外研究 Rotigotine has a 10-fold selectiv

6、ity for D3 (pKi 9.2) receptors compared with D2, D4 and D5 (pKi 8.5-8.0) anda 100-fold selectivity compared with D1 receptors (pKi 7.2). In functional studies, Rotigotine behaves as fullagonist at all dopamine receptors but notably the potency for stimulation of D1 receptors is similar to that forD2

7、 and D3 receptors (pEC50 respectively: 9.0, 9.4-8.6, 9.7) 1. Rotigotine (10 M) decreases the number ofTHir neurons by 40% in primary mesencephalic cell culture. Rotigotine (0.01 M) slightly protectsdopaminergic neurons against MPP+ toxicity, significantly protects dopaminergic neurons against roteno

8、ne-induced cell death, and significantly inhibits ROS production by rotenone 4.體內研究 In primed rats, Rotigotine (0.035, 0.1 and 0.35 mg/kg) induces contralateral turning behavior in a dosedependent manner. In drug naive rats, the turning behavior induced by Rotigotine, either alone or incombination w

9、ith SCH 39166, is reduced compared to primed rats 3.PROTOCOLKinase Assay 1 Binding assays are performed in 96-well polypropylene tubes in a final volume of 2mL for D1 and D4membranes and 1mL for D2, D3 and D5 membranes containing: 50L radioligand, 10L drug/buffer/non-specific binding, buffer (final

10、concentration 50mM Tris-HCl pH 7.4, MgCl2 2mM) and membranes (5gprotein for D2 and D3 and 25g protein for D1 and D5). Following 120min of incubation at 25C, boundradioligand is determined by rapid vacuum filtration through A/C glass fibre filters presoaked in 0.1%polyethylenimine. The filters are wa

11、shed four times with 2mL ice-cold ishing buffer (Tris-HCl 50mM, pH7.4at 4C) and retained radioactivity is determined by liquid scintillation counting.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Primed rats: Two weeks after the 6-OHDA lesions,

12、 rats are primed with apomorphine (0.5 mg/kg s.c.). RatsAdministration 3 showing less than 150 contralateral rotations during the 1 h testing period are excluded from the study. Threedays after priming, rats are divided into different experimental groups and treated with different doses of thedopami

13、ne receptor agonists (Rotigotine or pramipexole) alone or in combination with dopamine D1 (SCH39166) or D2 (eticlopride) receptor antagonists as reported: saline+Rotigotine (0.035 mg/kg s.c., n=9; 0.1mg/kg s.c., n=9; 0.35 mg/kg s.c., n=8); SCH 39166 (0.1 mg/kg s.c.)+Rotigotine (0.035 mg/kg s.c., n=5

14、; 0.1mg/kg s.c., n=7; 0.35 mg/kg s.c., n=5); eticlopride (0.1 mg/kg s.c.) + Rotigotine (0.1 mg/kg s.c., n=5; 0.352/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEmg/kg s.c., n=5); Saline+pramipexole (0.035 mg/kg s.c., n=5; 0.1 mg/kg s.c., n=12; 0.35 mg/kg s.c., n=7);SCH 39166 (0.1 mg/kg s.c.)+pramip

15、exole (0.035 mg/kg s.c., n=5; 0.1 mg/kg s.c., n=6; 0.35 mg/kg s.c., n=6);eticlopride (0.1 mg/kg s.c.)+pramipexole (0.1 mg/kg s.c., n=7; 0.35 mg/kg s.c., n=5).MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Wood M, et al. Rotigotine is a pot

16、ent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors. Br J Pharmacol.2015 Feb;172(4):1124-35.2. Scheller D, et al. The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinsons disease. Naunyn SchmiedebergsArch Pharmacol. 2009 Jan;379(1):73-86.3. Fenu S, et al. In vivo dopamine agonist properties of rotigotine: Role of D1 and D2 receptors. Eur J Pharmacol. 2016 Oct 5;788:183-91.4. Radad K, et al. Neuroprotective effect of rotigotine against complex I inhibitors, MPP+ and rotenone, in primary mesencepha