Orteronel-TAK-700-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEOrteronelCat.No.:HY-10505CASNo.:566939-85-3Synonyms:TAK-700分?式:C??H??N?O?分?量:307.35作?靶點:CytochromeP450作?通路:MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:14.29mg/mL(46.49mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.2536mL16.2681mL32.5362mL5mM0.6507mL3.2536mL6.5072mL10mM0.3254mL1.6268mL3.2536mL請根據產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?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?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儲存條件，適當保存；體內實驗的?作液，建議您現?現配，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沉淀、析出現象，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:≥1.43mg/mL(4.65mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.43mg/mL(4.65mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.43mg/mL(4.65mM);ClearsolutionBIOLOGICALACTIVITY?物活性Orteronel(TAK-700)?種?度選擇性的?17，20-裂解酶(17,20-lyase,CYP17)抑制劑，IC50值為38nM，對其選擇性對11-hydroxylase和CYP3A4的1000多倍[1][2]。IC50&TargetIC50:38nM(human17,20-lyase),54nM(rat17,20-lyase)體外研究Inmonkeyadrenalcells,orteronelinhibitstheACTHstimulatedproductionofDHEAandandrostenedionewithIC50of110nMand130nM,respectively.Moreover,OrteronelalsopotentlyinhibitsDHEAproductioninhumanadrenocorticaltumorlineH295RcellswithIC50of37nM[1].Invitro,orteronelshowsthepotentinhibitoryactivityagainstratandhumansteroid17,20-lyasewithIC50of54nMand38nM,respectively.WhileotherCYPisoformsincluding11-hydroxylaseandCYP3A4arenotsignificantlyaffectedbyOrteronel.InmicrosomesexpressinghumanCYPisoforms,Orteronelexhibitgreaterinhibitoryeffectson17,20-lyasewithIC50of19nMcomparedtotheotherCYPisoforms[2].體內研究Orteronel(1mg/kg,p.o.)resultsinfavorablepharmacokineticparameterswithTmax,Cmax,t1/2andAUC0-24hoursof1.7hours,0.147μg/mL,3.8hoursand0.727μg/mL,respectively[1].Incynomolgusmonkeys,oraltreatmentofOrteronelatadoseof1mg/kgmarkedlyreducesserumtestosteroneanddehydroepiandrosterone(DHEA)levels[2].PROTOCOLKinaseAssay[2]Rat11-hydroxylaseactivityismeasuredaccordingtoamethoddescribedforside-chaincleavageactivitypreviouslywithsomemodifications.Thereactionmixturecontained200mMmannitol,4.5mMHEPES,2.3mMpotassiumphosphate(pH7.4),0.1mMEDTA·2K,0.03%BSA(crystallized),4.5mMNADPH,11mMcalciumchloride,4μgofmitochondriaprotein,10nM[1,2-3H]-hydroxy-11-deoxycorticosterone(11-deoxycortisol)(NEN,dissolvedin0.02%Tween-80),and1-1000nMtestcompoundsinatotalvolumeof150μL.Theconcentrationsofreagentsareexpressedasthefinalconcentrationinthereactionmixture.Thetestcompoundsareseriallydilutedwithdimethylformamide,and1.5μLisaddeddirectlytothereactionmixture.After30minincubationat37°Cthereactionisterminatedbyadditionof400μLofethylacetateand100μLofdistilledwater,thenvortexedfor30sandbrieflycentrifuged.ThreehundredμLsoftheorganicphaseistransferredtoanewtubeandevaporateduntildryusingnitrogengas.Thesteroidsaredissolvedwith30μLofethylacetateandthewholevolumeisappliedtosilicagelTLCplates.Thesubstrateandtheproducts(11-deoxycortisolandcortisol)areseparatedinthetoluene-acetone(7:2)solventsystem.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalAdultmalecynomolgusmonkeyshousedinatemperature-controlledroom(23±2°C)witha12:12hlight/darkAdministration[2]cycle(illuminationfrom7:00amto7:00pm)areusedforthesingledosingexperiments.Thetestcompounds(+)-Orteroneland(?)-Orteronelaresuspendedin0.5%methylcelluloseandadministeredorallyatadoseof1mg/kg.Bloodsamplesarecollectedjustbeforedosingand8h(inapreliminarystudy)or2,5and10hafterdosing.Serumisstoredat?30°Cuntilassayedbyradioimmunoassay.ConcentrationsoftestosteroneandDHEAaredeterminedusingaTestosteroneI-125kitandaDHEARIAkit,respectively.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產品發表的科研?獻?SciRep.2016Aug26;6:32198.?Prostate.2017Dec;77(16):1550-1562.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].YamaokaM,etal.Orteronel(TAK-700),anovelnon-steroidal17,20-lyaseinhibitor:effectsonsteroidsynthesisinhumanandmonkeyadrenalcellsandserumsteroidlevelsincynomolgusmonkeys.JSteroidBiochemMolBiol.2012Apr;129(3-5):115-28.[2].Kaku,Tomohiro.,etal.Discoveryoforteronel(TAK-700),anaphthylmethylimidazolederivative,asahighlyselective17,20-lyaseinhibitorwithpotentialutilityinthetreatmentofprostatecancer.Fr