1、Product Data SheetAprepitantCat. No.: HY-10052CAS No.: 170729-80-3分式: CHFNO分量: 534.43作靶點: Neurokinin Receptor; Bacterial; HIV作通路: GPCR/G Protein; Neuronal Signaling; Anti-infection儲存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性數據體外實驗 DMSO : 100 mg/mL (

2、187.12 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.8712 mL 9.3558 mL 18.7115 mL5 mM 0.3742 mL 1.8712 mL 3.7423 mL10 mM 0.1871 mL 0.9356 mL 1.8712 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；旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month (protec

3、t from light)。-80C 儲存時，請在 6 個內使，-20C 儲存時，請在 1 個內使。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。以下溶解案都請先按照 In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄 的儲備液可以根據儲存條件，適當保存；體內實驗的作液，建議您現現配，當天 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沉淀、析出現象，可 以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5

4、 mg/mL (4.68 mM); Clear solution此案可獲得 2.5 mg/mL (4.68 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.68 mM); Clear solution此案可獲得 2.5 mg/mL (4.68 mM，飽和度未知) 的澄

5、溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。Page 1 of 2 www.MedChemEBIOLOGICAL ACTIVITY物活性 Aprepitant (MK-0869)選擇性和親和的神經激肽1受體拮抗劑，Kd 值為86 pM。IC & Target Kd: 86 pM (Neurokinin 1 receptor)1體外研究 Aprepitant decreases the metabolic activity with an estimated IC50 value

6、 of 20 M. Aprepitant induces cell-growthinhibition and G1 cell-cycle arrest. Aprepitant significantly induces apoptosis in Nalm-6 cells, and the apoptosis ismediated through caspase-3 activation. Aprepitant (20 M) induces p53 accumulation and expression of pro-apoptotic p53 target genes2. Aprepitant

7、 (1, 5, 10 M) inhibits HIV infection in MDM from both depressed and notdepressed HIV negative individuals ex vivo in a dose-dependent manner. IC90 value of aprepitant is equivalent to 10 M, and the IC50 value is about 5 M4.體內研究 Aprepitant prevents the increase of NK-1R expression induced by in vivo

8、NHP infection with B. burgdorferi.Aprepitant treatment prevents B. burgdorferi-induced increases in CCL2 protein levels in the CSF of NHPs. Aprepitant treatment prevents B. burgdorferi-induced increases in CCL2 and CXCL13 mRNA expression in the dorsal root gangliaof NHPs, prevents B. burgdorferi-ind

9、uced increases in CCL2, CXCL13, IL-17A, and IL-6 mRNA expression in the spinalcord of NHPs. Aprepitant treatment attenuates B. burgdorferi infection-induced reductions in astrocyteactivity/numbers1. Aprepitant (10 mg/kg, i.p.) significantly attenuates the CPP expression and locomotor activationprodu

10、ced by AMPH and cocaine in mice. In contrast, aprepitant significantly enhances the expression of CPPproduced by morphine while significantly suppressing the locomotor activity of the mice conditioned with morphine.Aprepitant does not induce significant CPP or conditioned place aversion or locomotor

11、 activation or suppression3.Aprepitant (125 mg/day, p.o.) results in 1 log reduction in plasma levels of viral RNA as compared to non-treatedcontrols4.PROTOCOLCell Assay 2 The inhibitory effect of aprepitant on metabolic activity of Nalm-6 cells is assessed by uptake of thiazolyl bluetetrazolium bro

12、mide (MTT) by viable cells. Cells are plated onto 96-well plates at a density of 5000 cells/well. Aftertreatment with aprepitant at 5, 10, 15, 20 and 30 M for 24, 36 and 48 h, the cells are further incubated with 100 Lof MTT (0.5 mg/mL) at 37C for 3 h. Untreated cells are defined as the control grou

13、p. Following solubilization ofprecipitated formazan with 100 L of DMSO, the optical densitometry is measured with an ELISA reader at awavelength of 578 nm.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Fifteen rhesus macaques are anesthetized an

14、d inoculated intrathecally with 1108 live spirochetes into the cisternaAdministration 1 magna, whereas five rhesus macaques are left uninfected and receive 1 mL of RPMI 1640 medium after removing anequivalent volume of CSF. The establishment of in vivo B. burgdorferi infection is confirmed by positi

15、ve culture fromat least necropsy tissue sample. The first set of animals are studied for 2 weeks and included two control animals (oneof which is treated with aprepitant), two infected and untreated animals, and two infected animals that are treatedwith aprepitant. The second set of animals are stud

16、ied for 4 weeks and included three control animals (one of whichis treated with aprepitant), five infected and untreated animals, and four infected animals treated with aprepitant.Animals receive an average dose of aprepitant of 28 6 mg/kg per day p.o. daily, and drug treatments are started 2days be

17、fore inoculation. These doses are consistent with standard veterinary regimens for the chosen drugs in NHP,and the 4-week duration of the study precludes the development of neural pathology that occurs at 8 weeksfollowing B. burgdorferi infection.MCE has not independently confirmed the accuracy of t

18、hese methods. They are for reference only.Page 2 of 3 www.MedChemEREFERENCES1. Martinez AN, et al. Aprepitant limits in vivo neuroinflammatory responses in a rhesus model of Lyme neuroborreliosis. J Neuroinflammation. 2017 Feb15;14(1):37.2. Bayati S, et al. Inhibition of tachykinin NK1 receptor using aprepitant induces apoptotic cell death and G1 arrest through Akt/p53 axis in pre-B acutelymphoblastic leukemia cells. Eur J Pharmacol. 2016 Nov 15;791:274-2