Docetaxel-RP-56976-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEDocetaxelCat.No.:HY-B0011CASNo.:114977-28-5Synonyms:RP-56976分⼦式:C₄₃H₅₃NO₁₄分⼦量:807.88作⽤靶点:Microtubule/Tubulin;Apoptosis;EndogenousMetabolite作⽤通路:CellCycle/DNADamage;Cytoskeleton;Apoptosis;MetabolicEnzyme/Protease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Ethanol:50mg/mL(61.89mM;Needultrasonic)DMSO:≥35mg/mL(43.32mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.2378mL6.1890mL12.3781mL5mM0.2476mL1.2378mL2.4756mL10mM0.1238mL0.6189mL1.2378mL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。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)1/4MasterofBioactiveMolecules—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(2.57mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(2.57mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(2.57mM);Clearsolution4.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(2.57mM);Clearsolution5.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(2.57mM);Clearsolution6.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(2.57mM);Clearsolution7.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.57mM);Clearsolution8.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.57mM);Clearsolution9.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.57mM);Clearsolution请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.57mM);Clearsolution请依序添加每种溶剂：10%EtOH>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥5mg/mL(6.19mM);Clearsolution请依序添加每种溶剂：10%EtOH>>90%cornoilSolubility:≥5mg/mL(6.19mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Docetaxel(RP-56976)⼀种微管解聚(microtubuledepolymerization)抑制剂，其IC50值为0.2μM。Docetaxel紫杉醇的半合成类似物，能减弱bcl-2和bcl-xL因表达的响。Docetaxel阻滞G2/M细胞周期，导致细胞凋亡(apoptosis)。Docetaxel具有抗肿瘤活性。IC50&TargetHumanEndogenousMetabolite体外研究Docetaxel(RP-56976)andGlufosfamide(GLU)singleandcombinedtreatmentsaffectthecellsviabilityinadose-dependentmanner.TheIC50ofGLUare70±4µMand86.8±8µMinPC-3andLNCaPcells;respectively.While,theIC50ofDocetaxelaloneisfoundtobe3.08±0.4nMand1.46±0.2nMinPC-3andLNCaPcells;respectively.Theco-treatmentofGLUwithDocetaxelisfoundtosynergizethecytotoxicityandtheIC50valuesaredecreasedtobe2.7±0.1nMand0.75±0.3nMinPC-3andLNCaPcells;respectively[1].IC50ofNCI-H460toDocetaxelat24his116nMandat72his30nM.AccordingtodatareportedinDTPDataSearch,themeanIC50ofNCI-60cellpaneltoDocetaxelis14-34nM[2].体内研究Infemalemice,theDocetaxel(RP-56976)-inducedintestinalapoptosisinthe14-hoursafterlighton(HALO)groupissignificantlygreaterthanthatinthe2-HALOgroup.Baxexpressionissignificantlyelevatedby2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDocetaxelinthe2-HALOgroup,butnotinthe14-HALOgroup.Ontheotherhand,cleavedCaspase-3expressionissignificantlyelevatedbyDocetaxelinthe14-HALOgroup,butnotinthe2-HALOgroup.TheexpressionsofWee1andphosphorylatedCKD1aresignificantlyelevatedafterdosingofDocetaxelat14HALO,butnotat2HALO.Inaddition,Docetaxelsignificantlyreducessurvivinexpressioninthe14-HALOgroupbutnotinthe2-HALOgroup.ThesurvivinexpressionlevelintheDocetaxel-treated14-HALOgroupissignificantlysmallerthanthatinthedrug-treated2-HALOgroup[3].Piperine(PIP)isadministratedviaintravenousbolusat3.5mg/kgandviaoraladministrationat35mg/kgand3.5mg/kg,whileDocetaxel(DOX)isintravenouslyadministratedat7mg/kgtoSprague-Daleyrats.Theco-administrationsofPIPat35mg/kgviaoraladministrationandDocetaxelat7mg/kgviaintravenousbolusadministrationinSprague-Dawleyrats.ThecombinationuseofPIPandDocetaxelresultsinasynergicincreaseofboththeirinvivoexposure[4].PROTOCOLCellAssay[1]Single-drugconcentration-responsecurvesareassessed.Seedingisdoneatadensityof2,000cells/wellforPC-3andLNCaP,in96-wellplates.Cellsaretreatedwitheachsingledrugandtheircombinationfor72hatdifferentdrugconcentrations.Docetaxelisusedatconcentrationsof0.1-1,000nM.GLUisusedatconcentrationsof0.1-300µm.CytotoxicityisassessedattheendofdrugexposureusingSRBassay.Following72hexposurethecellsarefixedwith10%trichloroaceticacid(150µL)for1hat4°C.Then,cellsarestainedfor10minatroomtemperaturewith0.4%SRBdissolvedin1%aceticacid.Theplatesarethenairdriedfor24handthedyeismadesolublewith150µLTris(10mM,PH7.4)for5minonashakerat1,600rpm.Absorbanceisthenmeasuredat545nMusingmicroplatereader.Resultsareexpressedastherelativepercentageofabsorbancecomparedtocontrol[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3][4]Five-week-oldmaleBalb/cmiceareused.Docetaxel(0,10,20,30,40,60,and80mg/kgperweek)isgivenonceaweekfor3weeksformice.Becausemorethan30mg/kgperweekofDocetaxelcausesbodyweightlossinmice,20mg/kgperweekofDocetaxelisjudgedtobethemaximumnontoxicdose.Docetaxel(20mg/kgperweek)isgiventomiceonceaweekfor3weeksatoneofthefollowingdifferentpoints(2,10,14,or22HALO).Seventy-twohoursafterthefinaldosingoftheagent,theintestinalmucosaofthesmallintestine(proximal8cm)isremoved,fixedin20NMildformsolution(containing8%formaldehydeinabufferedsolution),andembeddedinparaffinblocks,andsectionsof5μmareputonglassslides.Apoptosisisdetectedusingtheterminaldeoxynucleotidyltransferase-mediateddUTPnick-endlabeling(TUNEL)method,usingtheApopTagPeroxidaseInSituApoptosisDetectionKit.Rats[4]MaleSprague-Dawleyratswithbodyweightbetween230-250gandagebetween6-7weeksareused.About25SDratsaredividedintofivegroupsreceivingDocetaxel(7mg/kg,i.v.),PIP(35mg/kg,p.o.)andtheircombinedadministration(DOX+PIP)aswellasPIP(3.5mg/kg,p.o.)andPIP(3.5mg/kg,i.v.).Adaybeforethedrugadministrations,theratsareanesthetized.Rightjugularveiniscannulatedwithapolyethylenetubing(0.5mmID,1mm)forbloodcollection.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE户使⽤本产品发表的科研⽂献•SignalTransductTargetTher.2022Sep12;7(1):317.•ACSNano.2021Apr27;15(4):7179-7194.•EurUrol.2020Nov2;S0302-2838(20)30778-8.•Biomaterials.2September2022,121783.•ActaPharmSinB.2020June29.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].AttiaRT,etal.Thechemomodulatoryeffectsofgl