Rac-Opnurasib-Rac-JDQ-443-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemE(Rac)-OpnurasibCat.No.:HY-139612BCASNo.:2653201-38-6Synonyms:(Rac)-JDQ-443;(Rac)-NVP-JDQ443分⼦式:C₂₉H₂₈ClN₇O分⼦量:526.03作⽤靶点:DrugDerivative;Ras;PERK作⽤通路:Others;GPCR/GProtein;MAPK/ERKPathway;CellCycle/DNADamage储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性(Rac)-Opnurasib((Rac)-JDQ-443;(Rac)-NVP-JDQ443)Opnurasib(HY-139612)的消旋体。Opnurasib⼀种⼝服有效和选择性的共价KRASG12C抑制剂。Opnurasib具有抗肿瘤活性[1][2]。IC50&TargetKRasG12C体外研究OpnurasibtrapstheGDP-boundinactiveconformationofKRAS[1].Opnurasibpromotesdose-dependentreductionsofphosphorylatedERK(pERK)levelsandtheproliferationoftheKRASG12C-mutatedcelllinesNCI-H358andNCI-H2122,withIC50valuesof0.018and0.063μM,respectively[2].OpnurasibcovalentlyandselectivelybindsandinhibitsGDP-boundKRASG12CwithlowreversiblebindingaffinitytotheRASswitchIIpocket,andalsoinhibitsproliferationofKRASG12C-mutatedandKRASG12C/H95,G12C/R68S,andG12C/Y96double-mutantcelllines[2].体内研究Opnurasib(10-100mg/kg,Orally,dailyfor14days)showsantitumoractivityinKRASG12C-mutatedCDXmodels[2].Opnurasib(Orally,100mg/kg,daily(JDQ443)+7.5mg/kg,twicedaily(TNO155),for36days)showsgreatercellgrowthinhibitionorcellkillingcomparedwithsingle-agentJDQ443whencombinedwithTNO155[2].OpnurasibgeneratescategoricalantitumorresponsesinPDXmodelsofNSCLCandcolorectaltumorsthatareimprovedbycombinationtreatmentwithotheragents[2].REFERENCES1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].LIUBO,etal.PYRAZOLYLDERIVATIVESUSEFULASANTI-CANCERAGENTS.PatentWO2021120890A1.[2].WeissA,LorthioisE,BarysL,etal.Discovery,PreclinicalCharacterization,andEarlyClinicalActivityofJDQ443,aStructurallyNovel,PotentandSelective,CovalentOralInhibitorofKRASG12C.CancerDiscov.2022;candisc.0158.2022.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearchuseonly.Tel: