KRASG12C-IN-19-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEKRASG12CIN-19Cat.No.:HY-179484CASNo.:2915282-32-3分⼦式:C₃₃H₃₁FN₈O₂分⼦量:590.65作⽤靶点:ReactiveOxygenSpecies(ROS);ERK作⽤通路:Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κB;MAPK/ERKPathway;StemCell/Wnt储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性KRASG12CIN-19⼀种选择性KRASG12C抑制剂。KRASG12CIN-19对KRASG12C突变型⾮⼩细胞肺癌(NSCLC)细胞系H358展现出强效的抗增殖活性(IC50=7.6nM)，并能有效抑制下游ERK磷酸化(IC50=24.06nM)。KRASG12CIN-19对KRASG12V及KRASG12D突变型癌细胞(PANC1、Panc03.27、AsPC1和GP2d细胞)⽆显著抑制活性(IC50>10,000nM)。KRASG12CIN-19能快速与KRASG12V-GDP形成共价键，从⽽实现对下游KRAS通路的剂量依赖性抑制。KRASG12CIN-19可⽤于KRASG12C驱动的癌症研究，包括⾮⼩细胞肺癌、胰腺癌和结直肠癌[1]。IC50&TargetERK24.6nM(IC50)体外研究KRASG12CIN-19(compound8t)hasanexcellentlivermicrosomalstabilityinhumanandmouse(T1/2=188.2and112.3min,CLint=6.4and15.8mL/min/kg)[1].KRASG12CIN-19(4.88-312.5nM,72h)exhibitssignificantlylownanomolarantiproliferativeactivityagainstH358NSCLCcancercellswithanIC50valueof7.6nM[1].KRASG12CIN-19(4.88-312.5nM,72h)notexhibitscellularpotencyandpotencyagainstPANC-1(IC50>1000nM)(inKRASG12Vcell)andPanc03.27(IC50>1000nM)(indKRASG12Dcell),andpotencyagainstAsPC-1(IC50>1000nM)andGP2d(IC50>1000nM)cancercells[1].KRASG12CIN-19(4.88-312.5nM,3h)inducesdose-dependentsuppressionofERKphosphorylationonH358cellswithIC50of24.06nM[1].KRASG12CIN-19inhibitsERKphosphorylationinKRASG12C-mutantH358cells[1].KRASG12CIN-19(4.88-312.5nM)haslowtoxicitypotentialtowardhERGwithIC50>30μMinCHOcellline[1].1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体内研究KRASG12CIN-19(30mg/kg,p.o.,oncedailyfor29days)suppressesthegrowthofhumanH358NSCLCcell-derivedxenografttumorsbearingtheKRASG12CmutationinfemaleBALB/cmicewithoutinducingobservabletoxicsideeffects[1].AnimalModel:HumanH358NSCLCcell-derivedxenografttumorsbearingtheKRASG12CmutationinfemaleBALB/cmice(5-6weeksold)[1]Dosage:30mg/kgAdministration:p.o.,oncedailyfor29daysResult:Enhancedtumorregression,achievingatumorgrowthinhibition(TGI)rateof167.9%.Observednonotablechangesinbodyweight.REFERENCES[1].FangYang,etal.Design,synthesisandevaluationof1,2-dihydropyrido[2,3-d]pyrimidine-6‑carbonitrilederivativesasnovelcovalentinhibitorsforthetreatmentofKRASG12C-mutantNSCLC,BioorganicChemistry,McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications