Orteronel-TAK-700-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEOrteronelCat.No.:HY-10505CASNo.:566939-85-3Synonyms:TAK-700分⼦式:C₁₈H₁₇N₃O₂分⼦量:307.35作⽤靶点:CytochromeP450作⽤通路:MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:14.29mg/mL(46.49mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.2536mL16.2681mL32.5362mL5mM0.6507mL3.2536mL6.5072mL10mM0.3254mL1.6268mL3.2536mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥1.43mg/mL(4.65mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.43mg/mL(4.65mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1.43mg/mL(4.65mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Orteronel(TAK-700)⼀种⾼度选择性的⼈17，20-裂解酶(17,20-lyase,CYP17)抑制剂，IC50值为38nM，对其选择性对11-hydroxylase和CYP3A4的1000多倍[1][2]。IC50&TargetIC50:38nM(human17,20-lyase),54nM(rat17,20-lyase)体外研究Inmonkeyadrenalcells,orteronelinhibitstheACTHstimulatedproductionofDHEAandandrostenedionewithIC50of110nMand130nM,respectively.Moreover,OrteronelalsopotentlyinhibitsDHEAproductioninhumanadrenocorticaltumorlineH295RcellswithIC50of37nM[1].Invitro,orteronelshowsthepotentinhibitoryactivityagainstratandhumansteroid17,20-lyasewithIC50of54nMand38nM,respectively.WhileotherCYPisoformsincluding11-hydroxylaseandCYP3A4arenotsignificantlyaffectedbyOrteronel.InmicrosomesexpressinghumanCYPisoforms,Orteronelexhibitgreaterinhibitoryeffectson17,20-lyasewithIC50of19nMcomparedtotheotherCYPisoforms[2].体内研究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—您⾝边的抑制剂⼤师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.户使⽤本产品发表的科研⽂献•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