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MedKoo Biosciences/BMS-777607 (BMS-817378)/200527/2g

BMS-777607,alsoknownasBMS-817378andASLAN-002,aMettyrosinekinaseinhibitor,isaninhibitorofMETtyrosinekinasewithpotentialantineoplasticactivity.METtyrosinekinaseinhibitorBMS-777607bindstoc-Metprotein,orhepatocytegrowthfactorreceptor(HGFR),preventingbindingofhepatocytegrowthfactor(HGF)anddisruptingtheMETsignalingpathway;thisagentmayinducecelldeathintumorcellsexpressingc-Met.c-Met,areceptortyrosinekinaseoverexpressedormutatedinmanytumorcelltypes,playsanimportantroleintumorcellproliferation,survival,invasion,andmetastasis,andintumorangiogenesis.

MedKooCat#:200527
Name:BMS-777607(BMS-817378)
CAS#:1025720-94-8
ChemicalFormula:C25H19ClF2N4O4
ExactMass:512.10629
MolecularWeight:512.89
ElementalAnalysis:C,58.54;H,3.73;Cl,6.91;F,7.41;N,10.92;O,12.48


RelatedCAS#:1025720-94-8 1196681-44-3(deleted)  

Synonym:BMS817378;BMS817378;BMS-817378;BMS777607;BMS-777607;BMS777607;ASLAN002;ASLAN-002;ASLAN002.

IUPAC/ChemicalName:N-(4-((2-amino-3-chloropyridin-4-yl)oxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide.

InChiKey:VNBRGSXVFBYQNN-UHFFFAOYSA-N

InChiCode:InChI=1S/C25H19ClF2N4O4/c1-2-35-19-10-12-32(16-6-3-14(27)4-7-16)25(34)21(19)24(33)31-15-5-8-18(17(28)13-15)36-20-9-11-30-23(29)22(20)26/h4-13H,2H2,1H3,(H2,29,30)(H,31,33)

SMILESCode:O=C(C1=C(OCC)C=CN(C2=CC=C(F)C=C2)C1=O)NC3=CC=C(OC4=C(Cl)C(N)=NC=C4)C(F)=C3


TechnicalData

Appearance:
whitesolidpowder

Purity:
>98%(orrefertotheCertificateofAnalysis)

CertificateofAnalysis:
ViewCoA:previousbatch,Lot#TZC20131129
ViewCoA:currentbatch,Lot#TZC61220

QCData:
ViewQCdata:previousbatch,Lot#TZC20131129
ViewQCdata:currentbatch,Lot#TZC61220

SafetyDataSheet(MSDS):
ViewMaterialSafetyDataSheet(MSDS)

ShippingCondition:
Shippedunderambienttemperatureasnon-hazardouschemical.ThisproductisstableenoughforafewweeksduringordinaryshippingandtimespentinCustoms.

StorageCondition:
Dry,darkandat0-4Cforshortterm(daystoweeks)or-20Cforlongterm(monthstoyears)

Solubility:
SolubleinDMSOat40mg/mL,notsolubleinwater,notsolubleinethanol.

ShelfLife:
>2yearsifstoredproperly

DrugFormulation:
ThisdrugmaybeformulatedinDMSO

StockSolutionStorage:
0-4Cforshortterm(daystoweeks),or-20Cforlongterm(months).

HarmonizedSystemCode:
293490


References

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2:ChakedisJ,FrenchR,BABIckyM,JaquishD,HowardH,MoseE,LamR,HolmanP,MiyamotoJ,WalterscheidZ,LowyAM.AnovelproteinisoformoftheRONtyrosinekinasereceptortransformshumanpancreaticductepithelialcells.Oncogene.2015Oct19.doi:10.1038/onc.2015.384.[Epubaheadofprint]PubMedPMID:26477314;PubMedCentralPMCID:PMC4837108.

3:MüllerJ,KrijgsmanO,TsoiJ,RobertL,HugoW,SongC,KongX,PossikPA,Cornelissen-SteijgerPD,FoppenMH,KemperK,GodingCR,McDermottU,BlankC,HaanenJ,GraeberTG,RibasA,LoRS,PeeperDS.LowMITF/AXLratiopredictsearlyresistancetomultipletargeteddrugsinmelanoma.NatCommun.2014Dec15;5:5712.doi:10.1038/ncomms6712.PubMedPMID:25502142;PubMedCentralPMCID:PMC4428333.

4:NurhayatiRW,OjimaY,TayaM.BMS-777607promotesmegakaryocyticdifferentiationandinducespolyploidizationintheCHRF-288-11cells.HumCell.2015Apr;28(2):65-72.doi:10.1007/s13577-014-0102-2.Epub2014Oct11.PubMedPMID:25304900.

5:ZhangW,AiJ,ShiD,PengX,JiY,LiuJ,GengM,LiY.DiscoveryofnoveltypeIIc-MetinhibitorsbasedonBMS-777607.EurJMedChem.2014Jun10;80:254-66.doi:10.1016/j.ejmech.2014.04.056.Epub2014Apr21.PubMedPMID:24792774.

6:SzokolB,GyulaváriP,BaskaF,IbolyaK,GreffZ,SzántaiKC,ZoltánO,PetákI,AxelU,VantusT,KériG,OrfiL.[DevelopmentandbiochemicalcharacterizationofEGFR/c-Metdualinhibitors].ActaPharmHung.2013;83(4):121-33.Hungarian.PubMedPMID:24575658.

7:ZhangW,AiJ,ShiD,PengX,JiY,LiuJ,GengM,LiY.Discoveryofnovelc-Metinhibitorsbearinga3-carboxylpiperidin-2-onescaffold.Molecules.2014Feb24;19(2):2655-73.doi:10.3390/molecules19022655.PubMedPMID:24566328.

8:SharmaS,YaoHP,ZhouYQ,ZhouJ,ZhangR,WangMH.PreventionofBMS-777607-inducedpolyploidy/senescencebymTORinhibitorAZD8055sensitizesbreastcancercellstocytotoxicchemotherapeutics.MolOncol.2014May;8(3):469-82.doi:10.1016/j.molonc.2013.12.014.Epub2014Jan2.PubMedPMID:24444656.

9:TraoréT,CavagninoA,SaettelN,RadvanyiF,PiguelS,Bernard-PierrotI,StovenV,LegraverendM.NewaminopyrimidinederivativesasinhibitorsoftheTAMfamily.EurJMedChem.2013;70:789-801.doi:10.1016/j.ejmech.2013.10.037.Epub2013Oct22.PubMedPMID:24239626.

10:ZengJY,SharmaS,ZhouYQ,YaoHP,HuX,ZhangR,WangMH.SynergisticactivitiesofMET/RONinhibitorBMS-777607andmTORinhibitorAZD8055topolyploidcellsderivedfrompancreaticcancerandcancerstemcells.MolCancerTher.2014Jan;13(1):37-48.doi:10.1158/1535-7163.MCT-13-0242.Epub2013Nov14.PubMedPMID:24233399.

11:SharmaS,ZengJY,ZhuangCM,ZhouYQ,YaoHP,HuX,ZhangR,WangMH.Small-moleculeinhibitorBMS-777607inducesbreastcancercellpolyploidywithincreasedresistancetocytotoxicchemotherapyagents.MolCancerTher.2013May;12(5):725-36.doi:10.1158/1535-7163.MCT-12-1079.Epub2013Mar6.PubMedPMID:23468529.

12:VoortmanJ,HaradaT,ChangRP,KillianJK,SuuriniemiM,SmithWI,MeltzerPS,LucchiM,WangY,GiacconeG.Detectionandtherapeuticimplicationsofc-Metmutationsinsmallcelllungcancerandneuroendocrinetumors.CurrPharmDes.2013;19(5):833-40.PubMedPMID:22973954.

13:GujralTS,KarpRL,FinskiA,ChanM,SchwartzPE,MacBeathG,SorgerP.Profilingphospho-signalingnetworksinbreastcancerusingreverse-phaseproteinarrays.Oncogene.2013Jul18;32(29):3470-6.doi:10.1038/onc.2012.378.Epub2012Sep3.PubMedPMID:22945653;PubMedCentralPMCID:PMC3670968.

14:SuárezRM,ChevotF,CavagninoA,SaettelN,RadvanyiF,PiguelS,Bernard-PierrotI,StovenV,LegraverendM.InhibitorsoftheTAMsubfamilyoftyrosinekinases:synthesisandBIOLOGicalevaluation.EurJMedChem.2013Mar;61:2-25.doi:10.1016/j.ejmech.2012.06.005.Epub2012Jun12.PubMedPMID:22749189.

15:DaiY,SiemannDW.Constitutivelyactivec-MetkinaseinPC-3cellsisautocrine-independentandcanbeblockedbytheMetkinaseinhibitorBMS-777607.BMCCancer.2012May28;12:198.doi:10.1186/1471-2407-12-198.PubMedPMID:22639908;PubMedCentralPMCID:PMC3418572.

16:DaiY,BaeK,PampoC,SiemannDW.ImpactofthesmallmoleculeMetinhibitorBMS-777607onthemetastaticprocessinarodenttumormodelwithconstitutivec-Metactivation.ClinExpMetastasis.2012Mar;29(3):253-61.doi:10.1007/s10585-011-9447-z.PubMedPMID:22286523.

17:DaiY,SiemannDW.BMS-777607,asmall-moleculemetkinaseinhibitor,suppresseshepatocytegrowthfactor-stimulatedprostatecancermetastaticphenotypeinvitro.MolCancerTher.2010Jun;9(6):1554-61.doi:10.1158/1535-7163.MCT-10-0359.Epub2010Jun1.PubMedPMID:20515943.

18:SchroederGM,AnY,CaiZW,ChenXT,ClarkC,CorneliusLA,DaiJ,Gullo-BrownJ,GuptaA,HenleyB,HuntJT,JeyaseelanR,KamathA,KimK,LippyJ,LombardoLJ,ManneV,OppenheimerS,SackJS,SchmidtRJ,ShenG,StefanskiK,TokarskiJS,TrainorGL,WautletBS,WeiD,WilliamsDK,ZhangY,ZhangY,FargnoliJ,BorzilleriRM.DiscoveryofN-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide(BMS-777607),aselectiveandorallyefficaciousinhibitoroftheMetkinasesuperfamily.JMedChem.2009Mar12;52(5):1251-4.doi:10.1021/jm801586s.PubMedPMID:19260711.

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