Acelarin-NUC-1031-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAcelarinCat.No.:HY-100885CASNo.:840506-29-8Synonyms:NUC-1031分?式:C??H??F?N?O?P分?量:580.47作?靶點:DNA/RNASynthesis作?通路:CellCycle/DNADamage儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥36mg/mL(62.02mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.7227mL8.6137mL17.2274mL5mM0.3445mL1.7227mL3.4455mL10mM0.1723mL0.8614mL1.7227mL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。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?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：(為保證實驗結(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)實驗的?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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.58mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.58mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.58mM);ClearsolutionBIOLOGICALACTIVITY?物活性Acelarin（NUC-1031）?泛使?的核苷類似物吉西他濱的蛋?轉(zhuǎn)化和增強。IC50&TargetEC50：0.2nM(DNAsynthesisinhibitor)[1]體外研究Gemcitabineisanucleosideanaloguecommonlyusedincancertherapybutwithlimitedefficacyduetoahighsusceptibilitytocancercellresistance.Theadditionofaphosphoramidatemotiftothegemcitabinecanprotectitagainstmanyofthekeycancerresistancemechanisms.Aseriesofgemcitabinephosphoramidateprodrugsaresynthesizedandscreenedforcytostaticactivityinarangeofdifferenttumorcelllines.Amongthesynthesizedcompounds,NUC-1031isshowntobepotentinvitro.體內(nèi)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?邊的抑制劑?師www.MedChemEchangeandclinicalsymptomsfor2weeks[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?CancerChemotherPharmacol.2020Jun;85(6):1063-1078.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SlusarczykM,etal.ApplicationofProTidetechnologytogemcitabine:asuccessfulapproachtoovercomethekeycancerresistancemechanismsleadstoanewagent(NUC-1031)inclinicaldevelopment.JMedChem.2014Feb27;57(4):1