Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEATM-3507Cat.No.:HY-100948CASNo.:1861449-70-8分?式:C??H??FN?O?分?量:611.79作?靶點(diǎn):Myosin作?通路:Cytoskeleton儲存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:33.33mg/mL(54.48mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.6345mL8.1727mL16.3455mL5mM0.3269mL1.6345mL3.2691mL10mM0.1635mL0.8173mL1.6345mL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)。-80°C儲存時(shí)，請?jiān)?個?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個?內(nèi)使?。BIOLOGICALACTIVITY?物活性ATM-3507原肌球蛋?(tropomyosin)的?個有效抑制劑，其在?類??素瘤細(xì)胞系中的IC50值約為3.83-6.84μM。IC50&TargetIC50:3.83-6.84μM(tropomyosin,inhumanmelanomacelllines)[1].體外研究ThecelllinesdifferintheirrelativeexpressionofTpm3.1aswellasintheexpressionofotherisoforms.After1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEdetermingtheIC50concentrationsforTR100andATM-3507(CHLA-20:4.99±0.45μM,CHP-134:3.83±0.67μM,CHLA-90:6.84±2.37μM,SK-N-BE(2):5.00±0.42μM)ineachoftheneuroblastomacelllines,combinationsoftropomyosininhibitorsplusVincristinearetestedatlevelsofeachdrugalonethatkilllessthan50%oftheneuroblastomacells.ThecombinationsofbothtropomyosininhibitorsplusVincristinearecompletelycytotoxicinCHLA-20cells.All4celllinesshowsomedegreeofsynergyasdeterminedbytheChou–Talalaymethod.TheeffectisnotlimitedtothevincaalkaloidsasasimilarcombinationefficacyusingpaclitaxelplusTR100orATM-3507[1].體內(nèi)研究Themaximaltolerancedose(MTD)forTR100andATM-3507is60and150mg/kg,respectively.Itisfoundthatasignificantinhibitionoftumorgrowthandprolongationofanimalsurvivalusingeithercombinationcomparedwitheachmonotherapy.Themediansurvivalofmiceincreasedfrom18daysformicetreatedwithATM-3507tomorethan49daysformicetreatedwiththecombination.ItisalsofoundthattwiceweeklyintravenousadministrationofATM-3507alsoshowcombinationefficacy.Theimpactofeachtreatmentorthecombinationonbodyweightisminimal.DruglevelsaremeasuredfollowingtheintravenousadministrationofATM-3507at30mg/kginBalb/cmice(n=3pertimepoint).Themeanhalf-lifeofATM-3507is5.01hrsfortheterminaleliminationphase.ThemeanAUC0-tintheplasmais14,548ng/h/mL.TheCmaxofATM-3507is5,758ng/mLandthethet1/2is5.01h.TheobservedplasmaclearanceandvolumeofdistributionatsteadystateofATM-3507is33.8mL/min/kgand7.23L/kg,respectively[1].PROTOCOLCellAssay[1]The4melanomacelllinesCHLA-20,CHLA-90,SK-N-BE(2)andCHP-134areculturedat37°Cinahumidifiedincubatorat5%CO2andsupplemented100U/mLpenicillinand100mg/mLstreptomycin.Cellsareplatedin96-wellplatesat2000-4000cellsperwell,incubatedat37°CovernightandthentreatedwithvariousconcentrationsofTR100/ATM-3507(0.1-2.5μM)alone,TR100andATM-3507plusvariouschemotherapydrugs.Thecellviabilityisperformedonday3-5.Forthedosingscheduleoptimizationexperiment,TR100orVincristineisaddedatday1withtheotherbeingaddedatday2orbothTR100andVincristineareaddedonday1andplatesarereadatday5.Resultsarepresentedaspercentageofsurvivalcellscomparedwithcontrols.Allcellviabilityassaysareruninquadruplicateandthedatashownarerepresentativeofatleast2independentexperiments[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]Femaleathymicnudemice(age4-6weeks)areused.Micearesubcutaneouslyinjectedwith5.0×106CHLA-20cellsina150mLmixofPBSandMatrigel(2:1).ATM-3507andTR100areformulatedat15mg/mLin30%sulfobutyl-ether-b-cyclodextrinsodiumsalt(SBECD).VincristineisdissolvedinH2Oat0.125mg/kg.Whenthetumorsreachedvolumesof200-400mm3,micearerandomizedintothestudygroups.Animalsarefolloweduntiltheanimalreachedendpointcriteria.Tumorsizeismeasuredusingdigitalcaliperstwiceperweekandtumorvolumeiscalculated.Micearealsoweighedandobservedtwiceperweekforsignsofendpointcondition.MicethatdemonstratesignsoftoxicityorreachendpointcriteriaarehumanelyeuthanizedbyCO2asphyxiationandsubjectedtocervicaldislocationasthesecondarymethodofeuthanasia[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].CurrierMA,etal.IdentificationofCancer-TargetedTropomyosinInhibitorsandTheirSynergywithMicrotubuleDrugs.MolCancer