RG7112-RO5045337-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERG7112Cat.No.:HY-10959CASNo.:939981-39-2Synonyms:RO5045337分⼦式:C₃₈H₄₈Cl₂N₄O₄S分⼦量:727.78作⽤靶点:MDM-2/p53;E1/E2/E3Enzyme作⽤通路:Apoptosis;MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:200mg/mL(274.81mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.3740mL6.8702mL13.7404mL5mM0.2748mL1.3740mL2.7481mL10mM0.1374mL0.6870mL1.3740mL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:≥10mg/mL(13.74mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥10mg/mL(13.74mM);Clearsolution3.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥5mg/mL(6.87mM);Clearsolution4.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(3.44mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性RG7112有效的、选择性的、第⼀个⽤于临床的、可⼝服的、可透过⾎脑屏障的、MDM2-p53抑制剂，IC50值为18nM，结合到MDM2的KD值为11nM.IC50&TargetKd:11nM(MDM2)[1]体外研究RG7112(0-5μM)stabilizeswild-typep53andinducesp53signalingincancercells.RG7112effectivelyactivatesp53functionsincancercells[1][2].CellProliferationAssay[2]CellLine:SJSA1osteosarcomacells.Concentration:0-5μM.IncubationTime:0-60hours.Result:Dose-dependentlyinhibitedthegrowthandkilledSJSA1osteosarcomacellsexpressinghighlevelsofMDM2proteinduetoMDM2geneamplification.CellCycleAnalysis[2]CellLine:HCT116andSJSA1cells.Concentration:0-5μM.IncubationTime:48hours.Result:Inducedadose-dependentcellcycleblockinG1andG2/MphaseanddepletionoftheSphasecompartment.体内研究RG7112(25-200mg/kg,singleoraldose)activatesp53pathwayandinducesapoptosisintumorcellsinvivo[2].RG7112(100mg/kg,gavageonceperday,5days/weekfor3weeks)reducestumorgrowthrateandincreasessurvivalinGBMmodels[3].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:FemaleBalb/cnudemice[2].Dosage:25-200mg/kg.Administration:Orally,singledose.Result:AtthehighestdoselevelofRG7112(200mg/kg)only1.2%(±0.89SD)ofcellsincorporatedBrdUat24hpost-dosing,vs.14%(±1.83SD)ofvehicletreatedtumors.AnimalModel:GBMcellswereimplantedintothebrainofAthymicNudemice(7weeksoldfemales,10animals/group)[3].Dosage:100mg/kg.Administration:Oralgavage,onceperday,5days/weekfor3weeks.Result:ReducedtumorgrowthrateandincreasessurvivalinheterotopicandorthotopicanimalmodelsbearingMDM2-amplifiedGBM.户使⽤本产品发表的科研⽂献•AdvSci(Weinh).2020Aug5;7(19):2001041.•NatChemBiol.2018Feb;14(2):118-125.•EMBOJ.2019Oct15;38(20):e102096.•ClinCancerRes.2016Mar1;22(5):1185-96.•MaterSciEngCMaterBiolAppl.2020Mar;108:110403.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].VuB,etal.DiscoveryofRG7112:ASmall-MoleculeMDM2InhibitorinClinicalDevelopment.ACSMedChemLett.2013Apr2;4(5):466-9.[2].TovarC,etal.MDM2small-moleculeantagonistRG7112activatesp53signalingandregresseshumantumorsinpreclinicalcancermodels.CancerRes.2013Apr15;73(8):2587-97.[3].VerreaultM,etal.PreclinicalEfficacyoftheMDM2InhibitorRG7112inMDM2-AmplifiedandTP53Wild-typeGlioblastomas.ClinCancerRes.2016Mar1;22(5):1185-96.McePdfHeightCaution: