MS-444-BE-34776-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMS-444Cat.No.:HY-100685CASNo.:150045-18-4Synonyms:BE-34776分⼦式:C₁₃H₁₀O₄分⼦量:230.22作⽤靶点:Myosin作⽤通路:Cytoskeleton储存⽅式:-20°C,protectfromlight,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light,storedundernitrogen)溶解性数据体外实验DMSO:50mg/mL(217.18mM;Needultrasonic)1-Methyl-2-pyrrolidinone:20mg/mL(86.87mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM4.3437mL21.7184mL43.4367mL5mM0.8687mL4.3437mL8.6873mL10mM0.4344mL2.1718mL4.3437mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(protectfromlight,storedundernitrogen)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%1-Methyl-2-pyrrolidinone>>90%PBS1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:2mg/mL(8.69mM);Suspendedsolution;Needultrasonicandwarmingandheatto50°C2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2mg/mL(8.69mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2mg/mL(8.69mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性MS-444平滑肌肌球蛋⽩轻链激酶(MLCK)的抑制剂，IC50值为10μM。IC50&TargetIC50:10μM(myosin)[1].体外研究MS-444isasmallmoleculeRNA-bindingproteinHuR(ELAVL1)inhibitor.Colorectalcancer(CRC)cellsthatdisplayHuRoverexpressionaretreatedwithMS-444(1-100μM)for48hrwithIC50sof10.98±1.76μM,12.84±2.10μM,5.60±0.90μM,14.21±2.11μM,and10.98±1.24μMforHCT116,HCA-7,RKO,HT-29,andSW480cells,respectively.GrowthinhibitionisobservedinallCRClineswithIC50valuesrangingfrom5.60μMto14.21μMwithobservableeffectsseenat10μMMS-444.Contrastingeffectsareobservedusingnon-transformedsmallintestinal(RIE-1(IC50=40.70±3.53μM))andcolonic(YAMC(IC50=28.16±3.23μM))epithelialcells.Bothcelltypesdisplaypropertiesofnormalintestinalepithelialcellsandareproficientin3′UTRAU-richelements(ARE)-mRNAdecay.Bothnon-transformedcelllinesare~3-to4-foldlessresponsivetoMS-444-mediatedgrowthinhibition,withIC50valuesof40.70μMand28.16μM(P[2].体内研究TotesttheeffectsofMS-444onCRCcellgrowthinvivo,micebearingHCT116cellxenograftsreceiveIPinjectionsofMS-444(25mg/kgbw)orvehicleevery48hr.Overtheexperimentcourse,micedonotdisplayanyadverseeffectsandmaintainedsimilarweights.Anti-tumoreffectsofMS-444areobservedwithapproximately1.7-foldreductionintumorsize.MicetreatedwithMS-444showamarked2-to3-folddecreaseinmicrovesseldensity(MVD),indicatingtheanti-angiogenicpotentialofMS-444[2].PROTOCOLCellAssay[2]HumancolorectalcancercelllinesRKO,HCA-7,HCT116,HT-29,SW480andthenon-transformedintestinalepithelialcelllinesRIE-1,YAMCaretreatedwithvaryingconcentrationsofMS-444(1-100μM)for48hr.CellsurvivalismeasuredbyMTTassayafterincubationofcellsfor48hrwithMS-444.RelativecellsurvivaliscalculatedaspercentagenormalizedtoDMSOvehicle-treatedcellsandplottedtodetermineIC50[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]Athymicnude(Nu/Nu)miceareused.HCT116(2×106cells)andHCA-7(2.5×106)cellsresuspendedinPBSareinjectedintothedorsalsubcutaneoustissue.Mice(n=5pergroup)receiveintraperitoneal(IP)injectionsofMS-444(25mg/kg)dissolvedinPBS/5%N-MethylPyrrolidine(NMP)orvehiclecontrolevery48hr.Tumorgrowthisassayed[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].SatoshiNakanishi.etal.MS-444,anewinhibitorofmyosinlightchainkinasefromMicromonosporasp.KY7123.TheJournalOfAntibiotics.1995,48(9):948-951.[2].FernandoF.Blanco.etal,ImpactofHuRinhibitionbythesmallmoleculeMS-444oncolorectalcancercelltumorigenesis.Oncotarget.2016Nov8;7(45):7404