Acelarin-NUC-1031-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAcelarinCat.No.:HY-100885CASNo.:840506-29-8Synonyms:NUC-1031分⼦式:C₂₅H₂₇F₂N₄O₈P分⼦量:580.47作⽤靶点:DNA/RNASynthesis作⽤通路:CellCycle/DNADamage储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥36mg/mL(62.02mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.7227mL8.6137mL17.2274mL5mM0.3445mL1.7227mL3.4455mL10mM0.1723mL0.8614mL1.7227mL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。-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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.58mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.58mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.58mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Acelarin（NUC-1031）⼴泛使⽤的核苷类似物吉西他滨的蛋⽩转化和增强。IC50&TargetEC50：0.2nM(DNAsynthesisinhibitor)[1]体外研究Gemcitabineisanucleosideanaloguecommonlyusedincancertherapybutwithlimitedefficacyduetoahighsusceptibilitytocancercellresistance.Theadditionofaphosphoramidatemotiftothegemcitabinecanprotectitagainstmanyofthekeycancerresistancemechanisms.Aseriesofgemcitabinephosphoramidateprodrugsaresynthesizedandscreenedforcytostaticactivityinarangeofdifferenttumorcelllines.Amongthesynthesizedcompounds,NUC-1031isshowntobepotentinvitro.体内研究TheProTidedemonstratesasignificantreductionintumorsizeagainstpancreaticxenograftmodelscomparedwiththegemcitabinetreatedgroup,andlessadverseeffectsonbodyweight,indicatingabettersafetyprofile.DatastronglysuggeststhattheProTidesarenotreliantonkinasesornucleosidetransporterstoexerttheiractivityinsidetumorcellsandremainstableinthepresenceofdeaminases.TheProTideNUC-1031iscurrentlyadvancingthroughphaseI/IIclinicalstudiesandhasalreadygeneratedstrongpharmacokineticdatathatconfirmsignificantlyhigherintracellularlevelsofgemcitabinetriphosphate,togetherwithpromisingearlyefficacysignalsandafavorablesafetyprofile.Thephosphoramidatechemistryispotentiallyagreatsourceofnewandveryeffectiveanticanceragents,bringingaconsiderablearrayofadvancedtreatmentsspecificallydesignedtoovercomecancerresistancemechanismsthatwillbenefitagreaterproportionofpatients[1].PROTOCOLCellAssay[1]NUC-1031(5.0mg)isdissolvedinDMSO(0.050mL)andD2O(0.15mL).Afterrecordingthecontrol31PNMRat37°C,apreviouslydefrostedhuman,rat,ordogserum(0.30mL)isaddedtothesample,whichisnextsubmittedtothe31PNMRexperimentsat37°C.Thespectraarerecordedevery30minover13h.31PNMRrecordeddataareprocessedandanalyzedwiththeBrukerTopspin2.1program[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalBalb/cnudemicearefemale,sixtoeightweekold,withtheweightof20±2g.TheyareintraperitoneallyAdministration[1]givenNUC-1031(i.p0.228mmol/kg,132.3mg/kg,2×/WK)orvehiclefor2weeks.NUC-1031isdissolvedin40%Captisolsolution.(40%Captisolispreparedbydissolving20mgofCaptisolwithpurewater,andmadethefinalvolume50mL.Thesolventisfilteredwith0.22μmfilter).Micearemonitoreddailyforbodyweight2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEchangeandclinicalsymptomsfor2weeks[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CancerChemotherPharmacol.2020Jun;85(6):1063-1078.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SlusarczykM,etal.ApplicationofProTidetechnologytogemcitabine:asuccessfulapproachtoovercomethekeycancerresistancemechanismsleadstoanewagent(NUC-1031)inclinicaldevelopment.JMedChem.2014Feb27;57(4):1