UT-34-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEUT-34Cat.No.:HY-136242CASNo.:2168525-92-4分?式:C??H??F?N?O?分?量:356.27作?靶點:AndrogenReceptor作?通路:Others儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:250mg/mL(701.72mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.8069mL14.0343mL28.0686mL5mM0.5614mL2.8069mL5.6137mL10mM0.2807mL1.4034mL2.8069mL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(fù)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(dāng)?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(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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%salineSolubility:≥2.08mg/mL(5.84mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.84mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.84mM);ClearsolutionBIOLOGICALACTIVITY?物活性UT-34?種有效的，選擇性的，具有?服活性的第?代泛雄激素受體(AR)拮抗劑和降解劑，對野?型AR，F(xiàn)876L-AR和W741L-AR的IC50分別為211.7nM，262.4nM和215.7nM。UT-34與配體結(jié)合結(jié)構(gòu)域(LBD)和功能1(AF-1)結(jié)構(gòu)域結(jié)合，并需泛素蛋?酶體途徑來降解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]體外研究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?邊的抑制劑?師www.MedChemE體內(nèi)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