Ramelteon-TAK-375-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERamelteonCat. No.: HY-A0014CAS No.: 196597-26-9Synonyms: TAK-375分式: CHNO分量: 259.34作靶點(diǎn): Melatonin Receptor作通路: GPCR/G Protein; 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

2、 : 50 mg/mL (192.80 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 3.8559 mL 19.2797 mL 38.5594 mL5 mM 0.7712 mL 3.8559 mL 7.7119 mL10 mM 0.3856 mL 1.9280 mL 3.8559 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。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依

3、次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)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(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (9.64 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (9.64 mM); Clear solution1/3 Master of Sm

4、all Molecules 您邊的抑制劑師www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (9.64 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Ramelteon效選擇性的melatonin受體激動(dòng)劑，結(jié)合melatonin1和melatonin2受體的Ki值分別為14 和112 pM。IC50 & Target IC50: 14 pM (melatonin1), 112 pM (melatonin2) 1體外研究 Ramelteon shows very hig

5、h affinity for human melatonin1 and melatonin2 receptors (expressed in CHOcells), and chick forebrain melatonin receptors (consisting of melatonin1 and melatonin2 receptors) with Kivalues of 14.0, 112, and 23.1 pM, respectively. The affinity of ramelteon for hamster brain melatonin3 bindingsites is

6、extremely weak (Ki: 2.65 M) compared to melatonins affinity for the melatonin3 binding site Ki: 24.1nM). In addition, ramelteon shows no measurable affinity for a large number of ligand binding sites (includingbenzodiazepine receptors, dopamine receptors, opiate receptors, ion channels, and transpor

7、ters) and noeffect on the activity of various enzymes. Ramelteon inhibits forskolin-stimulated cAMP production in theCHO cells that express the human melatonin1 and melatonin2 receptors 1.體內(nèi)研究 Ramelteon significantly decreases wakefulness at doses of 0.001, 0.01, and 0.1 mg/kg, increases slow-wavesl

8、eep at doses of 0.001, 0.01, and 0.1 mg/kg, and increases rapid eye movement sleep at a dose of 0.1mg/kg in freely moving cats 2. Ramelteon is associated with reduced subjective sleep latency and improvedsleep quality. Ramelteon is associated with improvement in latency to persistent sleep, sleep ef

9、ficiency , andtotal sleep time 3. Ramelteon (10 mg/kg, i/p), administered close to the mid-point of the dark phase of theL:D cycle, significantly reduces NREM sleep latency (time from injection to the appearance of NREM sleep).Ramelteon also produces a short-lasting increase in NREM sleep duration,

10、but the NREM power spectrum isunaltered 4.PROTOCOLKinase Assay 1 cDNA encoding the human MT1 gene is introduced into CHO cells. Cells are harvested at confluence inCa2+ and Mg2+ free Hanks balanced salt solution containing 5 mM EDTA and collected by centrifugation.Cells are homogenized in ice-cold 5

11、0 mM TrisHCl buffer, washed twice, pelleted, and stored at -30C untilthe binding assays are conducted. Test compound and 40 pM 2- 125Imelatonin are mixed with the thawedhomogenate in a total volume of 1 mL and incubated at 25C for 150 min. The reaction is terminated byaddition of 3 mL of icecold buf

12、fer followed by vacuum filtration on a Whatman GF/B. The filter is washedtwice and radioactivity is counted by a g-counter 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats: Ramelteon is dissolved in DMSO at a concentration of 200 mg/mL, and

13、 diluted 100-fold in physiologicalAdministration 4 saline immediately before use. A different group of six implanted rats is given vehicle or ramelteon (10 mg/kgi.p.). The EEG and EMG are recorded for 1 hr before injection and then for a further 3.5 hr. All treatments are2/3 Master of Small Molecule

14、s 您邊的抑制劑師www.MedChemEadministered at 24:00 hr (near the mid-point of the dark phase of the L:D cycle) with a minimum of 72 hrseparating injections in the same animal. Each rat receives both treatments in a fully randomized, balancedcross-over design reducing the number of animals needed in the study

15、 4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶(hù)使本產(chǎn)品發(fā)表的科研獻(xiàn) Biol Pharm Bull. 2019;42(2):280-288.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Kato K, et al. Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2

16、receptor agonist. Neuropharmacology. 2005Feb;48(2):301-10.2. Miyamoto M, et al. The sleep-promoting action of ramelteon (TAK-375) in freely moving cats. Sleep. 2004 Nov 1;27(7):1319-25.3. Kuriyama A, et al. Ramelteon for the treatment of insomnia in adults: a systematic review and meta-analysis. Sleep Med. 2014Apr;15(4):385-92.4. Fisher SP, et al. Acute sleep-promoting action of the melatonin agonist, ramelteon, in