UT-34-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEUT-34Cat.No.:HY-136242CASNo.:2168525-92-4分⼦式:C₁₅H₁₂F₄N₄O₂分⼦量:356.27作⽤靶点:AndrogenReceptor作⽤通路:Others储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:250mg/mL(701.72mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.8069mL14.0343mL28.0686mL5mM0.5614mL2.8069mL5.6137mL10mM0.2807mL1.4034mL2.8069mL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。-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.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(5.84mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.84mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.84mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性UT-34⼀种有效的，选择性的，具有⼝服活性的第⼆代泛雄激素受体(AR)拮抗剂和降解剂，对野⽣型AR，F876L-AR和W741L-AR的IC50分别为211.7nM，262.4nM和215.7nM。UT-34与配体结合结构域(LBD)和功能1(AF-1)结构域结合，并需泛素蛋⽩酶体途径来降解AR。UT-34具有抗前列腺癌的功效。IC50&TargetIC50:211.7nM(Wild-typeAR),262.4nM(F876LAR)and215.7nM(W741LAR)[1]体外研究UT-34(3-10µM;24hours;LNCaPcells)treatmentinhibitstheexpressionofPSAandFKBP5andgrowthofLNCaPcellsstartingfrom100nMwithmaximumeffectobservedat10μM[1].UT-34(0.1-10µM;24hours;LNCaPcells)treatmentresultsinareductionofARlevelsat1000nMinLNCaPcells[1].TreatmentofZR-75-1cellsmaintainedinserum-containinggrowthmediumwithUT-34resultsindownregulationofARproteinlevels,butnotestrogenreceptor(ER)orprogesteronereceptor(PR)levels.Furthermore,inMDA-MB-453breastcancercellsthatexpressARandglucocorticoidreceptor(GR),UT-34inducesthedownregulationofAR,butnotGR[1].UT-34isaneffectivedegraderofbothARandAR-V7.LNCaP-ARV7cellsaretreatedfor24hoursinthepresenceof0.1nMR1881or10ng/mLDoxycycline.DoxycyclineinducestheexpressionofEDN2,whichisinhibitedbyUT-34,whileUT-34inhibitstheexpressionofR1881-inducedFKBP5geneexpression[1].CellViabilityAssay[1]CellLine:LNCaPcellsConcentration:3µM,10µMIncubationTime:24hoursResult:InhibitedtheexpressionofPSAandFKBP5andgrowthofLNCaPcellsstartingfrom100nMwithmaximumeffectobservedat10μM.WesternBlotAnalysis[1]CellLine:LNCaPcellsConcentration:0.1µM,1µM,10µMIncubationTime:24hoursResult:ResultedinareductionofARlevelsat1000nM.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体内研究UT-34(20-40mg/kg;oraladministration;daily;for14days;NSGmice)at20and40mg/kgreducestheseminalvesicleweightby10%-20%and50%-60%,respectively[1].UT-34inhibitsandrogen-dependenttissuessuchasprostateandseminalvesiclesinrats,andthegrowthofEnzalutamide-resistantcastration-resistantprostatecancer(CRPC)xenografts.UT-34alsoinducestumorregressioninintactimmunocompromisedrats[1].AnimalModel:Nonobesediabetic/severecombinedimmunodeficiencyGamma(NSG)miceinjectedwithMR49Fcells[1]Dosage:20mg/kgor40mg/kgAdministration:Oraladministration;daily;for14daysResult:Reducedtheseminalvesicleweight.REFERENCES[1].PonnusamyS,etal.OrallyBioavailableAndrogenReceptorDegrader,PotentialNext-GenerationTherapeuticforEnzalutamide-ResistantProstateCancer.ClinCancerRes.2019Nov15;25(22):6764-6780.[2].StoneL.UT-34:apromisingnewARdegrader.NatRevUrol.2019Nov;16(11):640.McePdfHeightCaution