ProductDescription
NVP-TAE684isanaminopyrimidine-based,ATP-competitiveinhibitorofALK(IC50,3nM)withadditionalactivityvsFlt3andTie2atvaluesof3nM,and12nM,respectively.DespiteALK"shighsequencehomologywithinsulinreceptorkinase(InsR),cellularInsRpotencyofNVP-TAE684inBa/F3Tel-Flt3andBa/F3Tel-Tie2celllineswas554nMand>1uM,respectively.[1]
Inhumananaplasticlarge-celllymphoma(ALCL)celllinesexpressingNPM-ALK,NVP-TAE684inhibitsproliferationofKarpas-29andSU-DHL-1celllineswithanIC50rangeof2-5nM.Additionally,NVP-TAE684inhibitsphosphorylationofdownstreamofbothERKandAktinKarpas-299cells,thusaidingintheconfirmationthatSTAT,RAS/FAR/MAPK,andPI3K/AktareactivatedbyNPM-ALKinALCLcelllines.
NVP-TAE684hasbeenshowntobeefficaciousinneuroblastomalineswithconstitutivelyactiveALKmutations(G1128A,I1171N,F1174L,R1192P,F1245C,R1275Q).[2]Additionally,NVP-TAE684iseffectiveincrizotinib-resistantEML4-ALKL1196Mmutantsaswellasothersecondarygatekeepermutations.[2]
Technicalinformation:
ChemicalFormula: | C30H40ClN7O3S | |
CAS#: | 761439-42-3 | |
MolecularWeight: | 614.2 | |
Purity: | >98% | |
Appearance: | PaleYellow | |
ChemicalName: | 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidine-2,4-diamine | |
Solubility: | Upto15mMinDMSO | |
Synonyms: | NVP-TAE684,TAE684,TAE-684 |
ShippingCondition:Theproductisshippedinaglassvialatambienttemperature.
Storagecondition:Forlongershelflife,storesolidpowderat4oCdesiccated,orstoreDMSOsolutionat-20oC.
Reference:
1. | Galkinetal.,IdentificationofNVP-TAE684,apotent,selective,andefficaciousinhibitorofNPM-ALK.Proc.Natl.Acad.Sci.2007,104(1),270-275.PubmedID:17185414 |
2. | Schonherretal.,ActivatingALKmutationsfoundinneuroblastomaareinhibitedbyCrizotinibandNVP-TAE684.Biochem.J.2011,440,405-413.PubmedID:21838707 |
3. | Katayamaetal.,Therapeuticstrategiestoovercomecrizotinibresistanceinnon-smallcelllungcancersharboringthefusiononcogeneEML4-ALK.Proc.Natl.Acad.Sci.2011,108(18),7535-7540.PubmedID:21502504 |