Oritinib-mesylate-SH-1028-mesylate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEOritinibmesylateCat.No.:HY-139920ACASNo.:2180164-79-6Synonyms:SH-1028mesylate分⼦式:C₃₂H₄₁N₇O₅S分⼦量:635.78作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Oritinib(SH-1028)mesylate⼀种选择性的、⼝服活性的、于嘧啶的不可逆EGFR抑制剂。IC50值为18nM。Oritinib(SH-1028)mesylate对EGFR敏感和耐药(T790M)突变表现出有效的活性。Oritinib(SH-1028)mesylate显抑制EGFR敏感和耐药突变肿瘤细胞的增殖[1]。IC50&TargetEGFR(WT)EGFRL858REGFRL861QEGFRL858R/T790M18nM(IC50)0.7nM(IC50)4nM(IC50)0.1nM(IC50)EGFRd746-750EGFRd746-1.4nM(IC50)750/T790M0.89nM(IC50)体外研究Oritinib(SH-1028)(72hours;10μmol/Landthe3-folddilution;ninetimes)mesylateselectivelyinhibitsEGFR-mutatedNCI-H1975,H3255andPC-9cells,withIC50valuesof3.93,9.39and7.63nM,respectively,whichismoresensitivethantheinhibitionofwild-typeEGFRinA431cells[1].CellProliferationAssay[1]CellLine:A431(EGFRWT),H3255(EGFRL858R),PC-9(EGFRd746-750)andNCI-H1975(EGFRL858R/T790M)cellsConcentration:0.001,0.01,0.1,1,and10μMIncubationTime:72hours1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:SelectivelyinhibitedEGFR-mutatedNCI-H1975,H3255andPC-9cells,withIC50sof3.93±1.12,9.39±0.88and7.63±0.18nmol/L,respectively,whichwereabout198-,83-and102-foldmoresensitivethantheinhibitionofwild-typeEGFRinA431cells(IC50=778.89±134.74nM).体内研究Oritinib(SH-1028)(p.o.;oncedailyforconsecutive14days;2.5-15mg/kg)mesylateinhibitsEGFR-mutanttumorprogressionbutnotwild-typeEGFRinvivo[1].Oritinib(SH-1028)(p.o.;oncedailyforconsecutive14days;2.5-15mg/kg)mesylateonlyinducesamoderatetumorgrowthinhibitioninA431(wild-typeEGFR)tumorxenografts,whilecausesprofoundandsustainedtumorshrinkageinbothNCI-H1975andPC-9xenograftmodelswithEGFRmutationswith5mg/kg/day[1].Oritinib(SH-1028)(p.o.;oncedailyforconsecutive14days;2.5-15mg/kg)mesylateshowsgoodbioavailability,andisdistributedextensivelyfromtheplasmatothetissueswithTmaxof1.5-2h,andAUC0–tvaluesofSH-1028inplasmaare118,300and931ng×h/mlonDay1,while272,308and993ng×h/mlonDay14[1].AnimalModel:Nu/Nufemalenudemice(6-8weeks)bearinghumanlungcancercelllines[1]Dosage:2.5,5,and15mg/kg(SH-1028)andcontrolgroup(osimertinib,5mg/kg)Administration:p.o.;oncedailyforconsecutive14daysResult:OnlyinducedamoderatetumorgrowthinhibitioninA431(wild-typeEGFR)tumorxenografts,whilecausedprofoundandsustainedtumorshrinkageinbothNCI-H1975andPC-9xenograftmodelswithEGFRmutationswith5mg/kg/day.REFERENCES[1].HanL,etal.SH-1028,AnIrreversibleThird-GenerationEGFRTKI,OvercomesT790M-MediatedResistanceinNon-SmallCellLungCancer.FrontPharmacol.2021;12:665253.McePdfHeightCaution:Producthasnotbeenfullyvalidatedfor