納曲吲哚鹽酸鹽作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetNaltrindole hydrochlorideCat. No.: HY-101177CAS No.: 111469-81-9分式: CHClNO分量: 450.96作靶點(diǎn): Opioid 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 : 188 mg/mL (416.89 mM)* means soluble, but saturation

2、 unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.2175 mL 11.0875 mL 22.1749 mL5 mM 0.4435 mL 2.2175 mL 4.4350 mL10 mM 0.2217 mL 1.1087 mL 2.2175 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；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)

3、動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.54 mM); Clear solution此案可獲得 2.5 mg/mL (5.54 mM，飽和度未知)

4、的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.54 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (5.54 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.

5、0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.54 mM); Clear solution此案可獲得 2.5 mg/mL (5.54 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Naltrindole hydrochloride效，

6、選擇性的多肽類 opioid 受體拮抗劑，Ki值為0.02 nM。IC & Target Ki: 0.02 nM ( opioid), 64 nM ( opioid), 66 nM ( opioid)1體外研究 Opioid drugs exert a wide spectrum of physiological and behavioral effects. These effects are mediated viamembrane-bound receptors, of which the best characterized are the kappa, delta, and mu r

7、eceptors1. Naltrindoleinhibits the proliferation of cultured human U266 MM cells in a time- and dose-dependent manner with an EC50 of 16M. Treatment of U266 cells with naltrindole significantly decreases the level of the active, phosphorylated form ofthe kinases, extracellular signal-regulated kinas

8、e and Akt, which may be related to its antiproliferative activity2.Naltrindole inhibits growth and induces apoptosis in the three characteristic SCLC cell lines, NCI-H69, NCI-H345, andNCI-H510. Naltrindole treatment reduces constitutive phosphorylation of Akt/PKB on serine 473 and threonine 308 ince

9、lls and also its downstream effectors glycogen synthase kinase-3 and the Forkhead transcription factors AFX andFKHR3.體內(nèi)研究 Naltrindole significantly decreases tumor cell volumes in human MM cell xenografts in severe combinedimmunodeficient mice2. In mice, naltrindole at 20 mg/kg s.c. antagonizes the

10、-selective agonist effect of D- Ser,Leu, Threnkephalin (DSLET) without blocking the antinociceptive effect of morphine or U50488H. Naltrindole is theonly highly selective antagonist that is active upon peripheral administration4. Acute naltrindole induces significantdecreases in external and total a

11、mbulation (horizontal activity) and rearing behaviour (vertical activity), as well as asignificant increase in grooming frequency. In animals chronically treated with naltrindole there is an increase in totalambulation one day after the discontinuation of the treatment5.PROTOCOLCell Assay 2 U266 cel

12、ls are plated in 96-well plates at 2000 cells per well in 100 L of RPMI 1640 medium, supplemented with 10%fetal bovine serum, 100 U/mL penicillin, and 100 g/mL streptomycin sulfate. Cells are incubated in quadruplicate inthe presence of the various antineoplastic agents to construct dose-response cu

13、rves, alone or in combination withvarious doses of naltrindole. At the end of the incubation 10 L of WST-1 cell proliferation reagent is added to eachwell, and the plates are returned to the incubator for 1 h. Absorbance is then measured2.MCE has not independently confirmed the accuracy of these met

14、hods. They are for reference only.Animal Rats:Administration 25 Effects of neonatal naltrindole treatments on open field activity is tested in 20-day old rats. The animals are injectedchronically with saline or naltrindole (1 mg/kg, s.c.) (from birth to day 19), and 1 day after the discontinuation o

15、f thistreatment are studied for the acute effects of naltrindole (1 mg/kg, i.p.)5.Page 2 of 3 www.MedChemEMice:Naltrindole is dissolved in distilled water to make a 3 mg/mL solution, and mice are injected with 10 mL/kg daily.Human RPMI 8226 multiple myeloma cells are inoculated subcutaneously into b

16、oth flanks of SCID mice (10 millioncells per flank). After 8 days, 12 mice are divided into two groups of six mice each: vehicle-injected and naltrindole-injected (30 mg/kg). Animals are dosed daily for 36 days, and body weights and xenograft tumors are measuredtwice a week with a digital caliper2.M

17、CE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Raynor K, et al. Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol. 1994 Feb;45(2):330-4.2. Mundra JJ, et al. Naltrindole inhibits human mult

18、iple myeloma cell proliferation in vitro and in a murine xenograft model in vivo. J Pharmacol Exp Ther.2012 Aug;342(2):273-87.3. Chen YL, et al. Inhibition of akt/protein kinase B signaling by naltrindole in small cell lung cancer cells.4. Portoghese PS, et al. Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist. Eur J Pharmacol. 1988 Jan 27;146(1):185-6.5. Fernndez B, et al. Postnatal naltrindole treatments induce behavioural modifications