MS-444-BE-34776-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMS-444Cat.No.:HY-100685CASNo.:150045-18-4Synonyms:BE-34776分?式:C??H??O?分?量:230.22作?靶點(diǎn):Myosin作?通路:Cytoskeleton儲存?式:-20°C,protectfromlight,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light,storedundernitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:50mg/mL(217.18mM;Needultrasonic)1-Methyl-2-pyrrolidinone:20mg/mL(86.87mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM4.3437mL21.7184mL43.4367mL5mM0.8687mL4.3437mL8.6873mL10mM0.4344mL2.1718mL4.3437mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(protectfromlight,storedundernitrogen)。-80°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，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.請依序添加每種溶劑：10%1-Methyl-2-pyrrolidinone>>90%PBS1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:2mg/mL(8.69mM);Suspendedsolution;Needultrasonicandwarmingandheatto50°C2.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2mg/mL(8.69mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2mg/mL(8.69mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性MS-444平滑肌肌球蛋?輕鏈激酶(MLCK)的抑制劑，IC50值為10μM。IC50&TargetIC50:10μM(myosin)[1].體外研究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].體內(nèi)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?邊的抑制劑?師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