Docetaxel-RP-56976-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEDocetaxelCat.No.:HY-B0011CASNo.:114977-28-5Synonyms:RP-56976分?式:C??H??NO??分?量:807.88作?靶點(diǎn):Microtubule/Tubulin;Apoptosis;EndogenousMetabolite作?通路:CellCycle/DNADamage;Cytoskeleton;Apoptosis;MetabolicEnzyme/Protease儲(chǔ)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)Ethanol:50mg/mL(61.89mM;Needultrasonic)DMSO:≥35mg/mL(43.32mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.2378mL6.1890mL12.3781mL5mM0.2476mL1.2378mL2.4756mL10mM0.1238mL0.6189mL1.2378mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month(protectfromlight)。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(2.57mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(2.57mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(2.57mM);Clearsolution4.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(2.57mM);Clearsolution5.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(2.57mM);Clearsolution6.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(2.57mM);Clearsolution7.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.57mM);Clearsolution8.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.57mM);Clearsolution9.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.57mM);Clearsolution請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.57mM);Clearsolution請(qǐng)依序添加每種溶劑：10%EtOH>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥5mg/mL(6.19mM);Clearsolution請(qǐng)依序添加每種溶劑：10%EtOH>>90%cornoilSolubility:≥5mg/mL(6.19mM);ClearsolutionBIOLOGICALACTIVITY?物活性Docetaxel(RP-56976)?種微管解聚(microtubuledepolymerization)抑制劑，其IC50值為0.2μM。Docetaxel紫杉醇的半合成類似物，能減弱bcl-2和bcl-xL因表達(dá)的響。Docetaxel阻滯G2/M細(xì)胞周期，導(dǎo)致細(xì)胞凋亡(apoptosis)。Docetaxel具有抗腫瘤活性。IC50&TargetHumanEndogenousMetabolite體外研究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].體內(nèi)研究Infemalemice,theDocetaxel(RP-56976)-inducedintestinalapoptosisinthe14-hoursafterlighton(HALO)groupissignificantlygreaterthanthatinthe2-HALOgroup.Baxexpressionissignificantlyelevatedby2/4MasterofBioactiveMolecules—您?邊的抑制劑?師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?邊的抑制劑?師www.MedChemE戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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