Aprepitant-MK-0869-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAprepitantCat. No.: HY-10052CAS No.: 170729-80-3Synonyms: MK-0869; MK-869; L-754030分式: CHFNO分量: 534.43作靶點(diǎn): Neurokinin Receptor作通路: GPCR/G Protein; Neuronal Signaling儲(chǔ)存式: 4C, protect from light* In solvent : -80C, 6 months; -20C,

2、 1 month (protect fromlight)溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (187.12 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)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(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。

3、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，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄的儲(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 (4.68 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.68 mM); Cle

4、ar solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Aprepitant (MK-0869)選擇性和親和的神經(jīng)激肽1受體拮抗劑，Kd 值為86 pM。IC50 & Target Kd: 86 pM (Neurokinin 1 receptor) 1體外研究 Aprepitant decreases the metabolic activity with an estimated IC50 value of 20 M. Aprepitant induces cell-growth i

5、nhibition and G1 cell-cycle arrest. Aprepitant significantly induces apoptosis in Nalm-6 cells, and theapoptosis is mediated through caspase-3 activation. Aprepitant (20 M) induces p53 accumulation andexpression of pro-apoptotic p53 target genes 2. Aprepitant (1, 5, 10 M) inhibits HIV infection in M

6、DM fromboth depressed and not depressed HIV negative individuals ex vivo in a dose-dependent manner. IC90 valueof aprepitant is equivalent to 10 M, and the IC50 value is about 5 M 4.體內(nèi)研究 Aprepitant prevents the increase of NK-1R expression induced by in vivo NHP infection with B. burgdorferi.Aprepit

7、ant 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 inthe dorsal root ganglia of NHPs, prevents B. burgdorferi-induced increases in CCL2, CXCL13, IL-17A, an

8、dIL-6 mRNA expression in the spinal cord of NHPs. Aprepitant treatment attenuates B. burgdorferi infection-induced reductions in astrocyte activity/numbers 1. Aprepitant (10 mg/kg, i.p.) significantly attenuates theCPP expression and locomotor activation produced by AMPH and cocaine in mice. In cont

9、rast, aprepitantsignificantly enhances the expression of CPP produced by morphine while significantly suppressing thelocomotor activity of the mice conditioned with morphine. Aprepitant does not induce significant CPP orconditioned place aversion or locomotor activation or suppression 3. Aprepitant

10、(125 mg/day, p.o.) results in1 log reduction in plasma levels of viral RNA as compared to non-treated controls 4.PROTOCOLCell Assay 2 The inhibitory effect of aprepitant on metabolic activity of Nalm-6 cells is assessed by uptake of thiazolyl bluetetrazolium bromide (MTT) by viable cells. Cells are

11、plated onto 96-well plates at a density of 5000 cells/well.After treatment with aprepitant at 5, 10, 15, 20 and 30 M for 24, 36 and 48 h, the cells are further incubatedwith 100 L of MTT (0.5 mg/mL) at 37C for 3 h. Untreated cells are defined as the control group. Followingsolubilization of precipit

12、ated formazan with 100 L of DMSO, the optical densitometry is measured with anELISA reader at a wavelength of 578 nm.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Fifteen rhesus macaques are anesthetized and inoculated intrathecally with 1108 l

13、ive spirochetes into theAdministration 1 cisterna magna, whereas five rhesus macaques are left uninfected and receive 1 mL of RPMI 1640 mediumafter removing an equivalent volume of CSF. The establishment of in vivo B. burgdorferi infection isconfirmed by positive culture from at least necropsy tissu

14、e sample. The first set of animals are studied for 2weeks and included two control animals (one of which is treated with aprepitant), two infected and untreatedanimals, and two infected animals that are treated with aprepitant. The second set of animals are studied for4 weeks and included three cont

15、rol animals (one of which is treated with aprepitant), five infected anduntreated animals, and four infected animals treated with aprepitant. Animals receive an average dose ofaprepitant of 286 mg/kg per day p.o. daily, and drug treatments are started 2 days before inoculation.2/3 Master of Small Mo

16、lecules 您邊的抑制劑師www.MedChemEThese doses are consistent with standard veterinary regimens for the chosen drugs in NHP, and the 4-weekduration of the study precludes the development of neural pathology that occurs at 8 weeks following B.burgdorferi infection.MCE has not independently confirmed the accu

17、racy of these methods. They are for reference only.REFERENCES1. Martinez AN, et al. Aprepitant limits in vivo neuroinflammatory responses in a rhesus model of Lyme neuroborreliosis. JNeuroinflammation. 2017 Feb 15;14(1):37.2. Bayati S, et al. Inhibition of tachykinin NK1 receptor using aprepitant in

18、duces apoptotic cell death and G1 arrest through Akt/p53 axis inpre-B acute lymphoblastic leukemia cells. Eur J Pharmacol. 2016 Nov 15;791:274-283.3. Mannangatti P, et al. Differential effects of aprepitant, a clinically used neurokinin-1 receptor antagonist on the expression of conditionedpsychostimulant versus opioid reward. Psychopharmacology (Berl). 2017 Feb;234(4):695-705.4. Barrett JS, et al. Pharmacologic rationale for the NK1R antagonis