XY018-DataSheet-生命科学试剂-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEXY018Cat.No.:HY-120210CASNo.:1873358-87-2分⼦式:C₂₃H₁₅F₇N₂O₄分⼦量:516.37作⽤靶点:ROR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:100mg/mL(193.66mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9366mL9.6830mL19.3660mL5mM0.3873mL1.9366mL3.8732mL10mM0.1937mL0.9683mL1.9366mL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，并请注意储备液的保存⽅式和期限。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，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的⼯作液，建议您现⽤现配，当天使⽤；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分⽐指该溶剂在您配制终溶液中的体积占⽐)：1.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.84mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.84mM);ClearsolutionBIOLOGICALACTIVITY1/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemE⽣物活性XY018⼀种有效的ROR-γ选择性拮抗剂。XY018作⽤于293T细胞，抑制ROR-γ活性，EC50为190nM。XY018与ROR-γ疏⽔配体结合域(LBD)结合[1]。IC50&TargetROR-γROR-α0.19μM(IC50,in293Tcells)7.57μM(IC50,in293Tcells)体外研究XY018(0.07-10μM;4days)inhibitCRPCtumorsC4-2Bcellsgrowthandsurvival[1].XY018inhibitsGal4-RORγ-LBDandGal4-RORα-LBDwithIC50sof0.19±0.02and7.57μMin293Tcells,respectively[2].XY018showsanti-proliferationeffectsagainsttheprostatecancercelllinesLNCaP,22Rv1,C4-2B,DU145,andPC-3withIC50sof5.14±0.36,9.00±0.33,9.20,28.43±0.89,and11.14±1.78μM,respectively[2].CellViabilityAssay[1]CellLine:CRPCtumorsC4-2BConcentration:0.07,0.15,0.31,0.62,1.25,2.5,5,and10μMIncubationTime:4daysResult:Inhibitedgrowthandsurvival.体内研究XY018(5mg/kg;intraperitoneallyi.p.;fivetimesperweekfor23days)inhibitCRPCtumorgrowthinmice[1].XY018(10mg/kgorallyor2mg/kgintravenously)exhibitsreasonablepharmacokineticsprofilesinSDrats[2].AnimalModel:Four-week-oldmaleSCIDC.B17mice(forC4-2BandVCaP)orBALB/cnu/nuathymicmice(for22Rv1andPC-3)[1]Dosage:5mg/kgAdministration:Treatedintraperitoneally(i.p.);fivetimesperweekfor23daysResult:Tumorgrowthinhibition.AnimalModel:SpragueDawleyrats[2]Dosage:10mg/kg(po;1mg/mL);2mg/kg(iv;0.4mg/mL)(PharmacokineticAnalysis)Administration:Orallyadministrated(10mg/kg)andintravenouslyadministrated(2mg/kg);singledoseResult:HighplasmaexposureAUC(0–∞)valueof6444(μg/L·h),half-life(T1/2=7.67±2.36h)andmaximumplasmaconcentration(Cmax)valueof839(μg/L)aftera2mg/kgivadministration.Demonstratedarelativelyloworalbioavailabilityof19%afteranoraladministration.2/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].JunjianWang,etal.ROR-γDrivesAndrogenReceptorExpressionandRepresentsaTherapeuticTargetinCastration-ResistantProstateCancer.NatMed.2016May;22(5):488-96.[2].YanZhang,etal.DiscoveryandCharacterizationofXY101,aPotent,Selective,andOrallyBioavailableRORγInverseAgonistforTreatmentofCastration-ResistantProstateCancer.JMedChem.2019May9;62(9):4716-4730.McePdfHeightCaution:Producthasnotbeenfullyval