PR-104A-SN-27858-DataSheet-生命科學試劑-MedChemExpressVIP

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPR-104ACat.No.:HY-14572CASNo.:680199-06-8Synonyms:SN27858分?式:C??H??BrN?O?S分?量:499.29作?靶點:DNAAlkylator/Crosslinker;DrugMetabolite作?通路:CellCycle/DNADamage;MetabolicEnzyme/Protease儲存?式:Pureform-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:250mg/mL(500.71mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.0028mL10.0142mL20.0284mL5mM0.4006mL2.0028mL4.0057mL10mM0.2003mL1.0014mL2.0028mL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?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：(為保證實驗結果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥6.25mg/mL(12.52mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥6.25mg/mL(12.52mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥6.25mg/mL(12.52mM);ClearsolutionBIOLOGICALACTIVITY?物活性PR-104A(SN27858)磷酸鹽前藥PR-104的醇代謝物。PR-104A?種缺氧選擇性的DNA交聯(lián)劑/DNA損傷劑，也?種細胞毒素。具有抗腫瘤活性[1]。PR-104A在缺氧條件下通過1-電?NADPH:細胞?素P450氧化還原酶代謝?？?于復發(fā)/難治性T系急性淋巴細胞??病(T-ALL)的研究[2]。體外研究PR-104A(1-100uM)showsantiproliferativepotencyinapanelof10humancarcinomacelllinesfollowing4hoursexposuresunderaerobicandhypoxicconditionswiththelowestIC50(0.51μM)inH460non-smallcelllungcancercellsandhighest(7.3μM)inPC3prostatecells[1].ThephosphateesterPR-104israpidlyconvertedinvivotothealcoholPR-104A,anitrogenmustardprodrugthatismetabolisedtohydroxylamine(PR-104H)andamine(PR-104M)DNAcrosslinkingagentsbyone-electronreductasesinhypoxiccellsandbyaldo-ketoreductase1C3independentlyofoxygen[3].CellProliferationAssay[1]CellLine:HT29,HCT116,C33ASiHaA549,H460,H1299,PC3,SKOV3,A375cellsConcentration:0,1,10,100uMIncubationTime:4hoursunderaerobicorhypoxicconditionsResult:ThelowestIC50(0.51μM)inH460non-smallcelllungcancercellsandhighest(7.3μM)inPC3prostatecells.體內(nèi)研究Thephosphateester“pre-prodrug”PR-104iswelltoleratedinmiceandconvertedrapidlytothecorrespondingprodrugPR-104A.H460xenograftsshowssignificantsensitivitytoPR-104(totaldose3.2mmol/kg)[1].AnimalModel:Specificpathogen-freehomozygousnude(CD1-Foxn1nu)micewithH460xenografts[1]Dosage:Daily(0.23mmol/kg/dose;qd×14)orweekly(1.07mmol/kg/dose;qw×3)Administration:I.p.Result:Thesingle-agentactivityagainstH460tumorsrefractorytodocetaxel,cisplatin,gemcitabine,andcyclophosphamidewasparticularlystriking.Comparedadaily(qd×14)versusweekly(qw×3)scheduleagainstthechemoresistantH460xenograftmodelusingthesametotaldose(3.2mmol/kg)over14days,whichwas2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEwelltoleratedusingbothschedules.REFERENCES[1].AdamVPatterson,etal.Mechanismofactionandpreclinicalantitumoractivityofthenovelhypoxia-activatedDNAcross-linkingagentPR-104.ClinCancerRes.2007Jul1;13(13):3922-32.[2].DonyaMoradiManesh,etal.AKR1C3isabiomarkerofsensitivitytoPR-104inpreclinicalmodelsofT-cellacutelymphoblasticleukemia.Blood.2015Sep3;126(10):1193-202.[3].McKeageMJ,etal.AphaseItrialofPR-104,apre-prodrugofthebioreductiveprodrugPR-104A,givenweeklytosolidtumourpatients.BMCCancer.2011;11:432.Published2011Oct7.McePdfHeightCaution:Pro