ATM-3507-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEATM-3507Cat.No.:HY-100948CASNo.:1861449-70-8分⼦式:C₃₇H₄₆FN₅O₂分⼦量:611.79作⽤靶点:Myosin作⽤通路:Cytoskeleton储存⽅式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性数据体外实验DMSO:33.33mg/mL(54.48mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6345mL8.1727mL16.3455mL5mM0.3269mL1.6345mL3.2691mL10mM0.1635mL0.8173mL1.6345mL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)。-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。BIOLOGICALACTIVITY⽣物活性ATM-3507原肌球蛋⽩(tropomyosin)的⼀个有效抑制剂，其在⼈类⿊⾊素瘤细胞系中的IC50值约为3.83-6.84μM。IC50&TargetIC50:3.83-6.84μM(tropomyosin,inhumanmelanomacelllines)[1].体外研究ThecelllinesdifferintheirrelativeexpressionofTpm3.1aswellasintheexpressionofotherisoforms.After1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师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].体内研究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—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].CurrierMA,etal.IdentificationofCancer-TargetedTropomyosinInhibitorsandTheirSynergywithMicrotubuleDrugs.MolCancer