Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEZosuquidarCat.No.:HY-15255CASNo.:167354-41-8Synonyms:RS33295-198;LY-335979分?式:C??H??F?N?O?分?量:527.6作?靶點(diǎn):P-glycoprotein作?通路:MembraneTransporter/IonChannel儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:8.33mg/mL(15.79mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.8954mL9.4769mL18.9538mL5mM0.3791mL1.8954mL3.7908mL10mM0.1895mL0.9477mL1.8954mL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。-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.請(qǐng)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:≥0.83mg/mL(1.57mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:0.83mg/mL(1.57mM);Suspendedsolution;Needultrasonic3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥0.83mg/mL(1.57mM);ClearsolutionBIOLOGICALACTIVITY?物活性Zosuquidar(LY335979)?種P-糖蛋?(P-gp)抑制劑(Ki=59nM)。Zosuquidar具有抗腫瘤活性，并可?于急性?髓性??病(AML)的研究。體外研究Zosuquidar(0.3μM;48h)treatmentenhancesthecytotoxicityofDNR(substratesforP-glycoproteins)inP-glycoproteinsactivecelllines[2].Zosuquidar(5-16μM;72h)treatmentaloneshowshighcytotoxicconcentrationtodrug-sensitiveandMDRcelllines[1].CellCytotoxicityAssay[2]CellLine:K562andHL60cellsConcentration:0.3μMIncubationTime:48hoursResult:EnhancedthecytotoxicityofDNR(substratesforP-glycoproteins)inK562/DOXcellsmorethan45.5-fold.CellCytotoxicityAssay[1]CellLine:CCRF-CEM,CEM/VLB100,P388,P388/ADR,MCF7,MCF7/ADR,2780,2780AD,UCLA-P3,UCLA-P3.003VLBcellsConcentration:5-16μMIncubationTime:72hoursResult:ShowedIC50sof6,7,15,8,7,15,11,16,>5,>5μMforCCRF-CEM,CEM/VLB100,P388,P388/ADR,MCF7,MCF7/ADR,2780,2780AD,UCLA-P3,UCLA-P3.003VLBcells,respectively.體內(nèi)研究Zosuquidar(intraperitonealinjection;30,10,3,or1mg/kg;oncedaily;5d)treatmentshowsasignificantincreaseinlifespan[1].Zosuquidar(intraperitonealinjection;30mg/kg;oncedaily;5d)treatmentshowsthepotentiationwithacombinedofDoxorubicin[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:MiceimplantedwithP388/ADRtumors[1]Dosage:30,10,3,or1mg/kgAdministration:Intraperitonealinjection;30,10,3,or1mg/kg;oncedaily;5daysResult:ExihibitedasignificantlyincreasedsurvivalcomparedtothegrouptreatedwithDoxorubicinalone(P<0.001).AnimalModel:MiceimplantedwithP388orP388/ADRmurineleukemiacells[1]Dosage:30mg/kgAdministration:Intraperitonealinjection;30mg/kg;oncedaily;5daysResult:ObservedsignificantantitumoractivityagainsttheMDRP388/ADRcelllineswhenmiceweretreatedwithacombineddoseof30mg/kgLY335979and1mg/kgDoxorubicin(P=0.1).戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CancerCell.2017Apr10;31(4):501-515.e8.?AntiviralRes.2021Jun28;105124.?BloodAdv.2020Oct27;4(20):5062-5077.?BiomedPharmacother.2020Sep;129:110506.?Pharmaceutics.2021,13(4),559.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].AHDantzig,etal.ReversalofP-glycoprotein-mediatedmultidrugresistancebyapotentcyclopropyldibenzosuberanemodulator,LY335979.CancerRes.1996Sep15;56(18):4171-9.[2].RuopingTang,etal.ZosuquidarrestoresdrugsensitivityinP-glycoproteinexpressingacutemyeloidleukemia(AML).BMCCancer.2008Feb13;8:51.[3].LarryDCripe,etal.Zosuquidar,anovelmodulatorofP-glycoprotein,doesnotimprovetheoutcomeofolderpatientswithnewlydiagnosedacutemyeloidleukemia:arandomized,placebo-controlledtrialoftheEasternCooperativeOncologyGroup3999.BloodMcePdfHeig