RG7112-RO5045337-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERG7112Cat.No.:HY-10959CASNo.:939981-39-2Synonyms:RO5045337分?式:C??H??Cl?N?O?S分?量:727.78作?靶點(diǎn):MDM-2/p53;E1/E2/E3Enzyme作?通路:Apoptosis;MetabolicEnzyme/Protease儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:200mg/mL(274.81mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.3740mL6.8702mL13.7404mL5mM0.2748mL1.3740mL2.7481mL10mM0.1374mL0.6870mL1.3740mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)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:≥10mg/mL(13.74mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥10mg/mL(13.74mM);Clearsolution3.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥5mg/mL(6.87mM);Clearsolution4.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(3.44mM);ClearsolutionBIOLOGICALACTIVITY?物活性RG7112有效的、選擇性的、第?個(gè)?于臨床的、可?服的、可透過(guò)?腦屏障的、MDM2-p53抑制劑，IC50值為18nM，結(jié)合到MDM2的KD值為11nM.IC50&TargetKd:11nM(MDM2)[1]體外研究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.體內(nèi)研究RG7112(25-200mg/kg,singleoraldose)activatesp53pathwayandinducesapoptosisintumorcellsinvivo[2].RG7112(100mg/kg,gavageonceperday,5days/weekfor3weeks)reducestumorgrowthrateandincreasessurvivalinGBMmodels[3].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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: