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

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEOritinibCat.No.:HY-139920CASNo.:2035089-28-0Synonyms:SH-1028分⼦式:C₃₁H₃₇N₇O₂分⼦量:539.67作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:125mg/mL(231.62mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.8530mL9.2649mL18.5298mL5mM0.3706mL1.8530mL3.7060mL10mM0.1853mL0.9265mL1.8530mL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。BIOLOGICALACTIVITY⽣物活性SH-1028⼀种不可逆的第三代EGFRTKI，可克服T790M介导的⾮⼩细胞肺癌耐药。SH-1028EGFR激酶活性的突变选择性抑制剂，抑制EGFRWT、EGFRL858R、EGFRL861Q、EGFRL858R/T790M、EGFRd746-750和EGFRd746-750/T790M激酶，IC50值分别为18、0.7、4、0.1、1.4和0.89nM。1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIC50&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)bindsirreversiblytoEGFRkinasebytargetingcysteine-797residueintheATPbindingsiteviacovalentbondformation[1].Oritinib(0.001-10μM)potentlyandselectivelytargetsmutantEGFRcelllinesinvitro[1].Oritinib(0.1μM)continuouslyinhibitsthephosphorylationofEGFRinPC-9andNCI-H1975cellsatlowerconcentrationsorevendrug-freeforatleast6h[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:72hoursResult: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OraladministrationofOritinibatadailydoseof5mg/kgsignificantlyinhibitsproliferationoftumorcellswithEGFRsensitivemutation(exon19del)andresistantmutation(T790M)forconsecutive14days,withnoTKI-inducedweightlossinmousexenograftmodels[1].Oritinibshowsgoodbioavailability,andisdistributedextensivelyfromtheplasmatothetissues[1].AnimalModel:6-8weeksoldfemalemicebearingNCI-H1975andA431xenograftmodels[1]Dosage:2.5,5,and15mg/kgAdministration:Orallyadministratedoncedailyforconsecutive14daysResult:LedtoasignificantinhibitionoftumorcellgrowthinbothPC-9(exon19del)andNCI-H1975(L858R/T790M)xenograftmodels.AnimalModel:NCI-H1975tumor-bearingmice[1]Dosage:2.5,5,and15mg/kg(PharmacokineticAnalysis)Administration:Oraladministrationfor1dayor14consecutivedays.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:TheTmaxis1.5-2h,indicatingrapidlydistributedintotissues,includinglungtumortissues.TheAUC0–tvaluesinplasmawere118,300and931ng×h/mLonDay1,while272,308and993ng×h/mlonDay14,respectively.REFERENCES[1].LuweiHan,etal.SH-1028,AnIrreversibleThird-GenerationEGFRTKI,OvercomesT790M-MediatedResistanceinNon-SmallCellLungCancer.FrontPharmacol.2021Apr27;12:665253.McePdfHeightCaution:Producthasnotbeenful