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MedKoo Biosciences/CGK733/406386/200mg
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CGK733isanATMinhibitorandATRinhibitor,whichsignificantlyenhancedtaxol-inducedcytotoxicityinHBV-positiveHepG2.2.15cells.ThemechanismliesinCGK733triggerstheformationofmultinucleatedcellsthuspromotestheprematuremitoticexitoftaxol-inducedmitotic-damagedcellsthroughmultinucleationandmitoticcatastropheinHBV-positiveHepG2.2.15cells.TheseresultssuggestthatCGK733couldpotentiallyreversethetaxolresistanceinHBV-positiveHCCcellsandmaysuggestanovelstrategytotreatHBV-infectedHCCpatients.MedKooCat#:406386Name:CGK733CAS#:905973-89-9ChemicalFormula:C23H18Cl3FN4O3SExactMass:554.01492MolecularWeight:555.84ElementalAnalysis:C,49.70;H,3.26;Cl,19.13;F,3.42;N,10.08;O,8.64;S,5.77Synonym:CGK733;CGK-733;CGK733.IUPAC/ChemicalName:2,2-diphenyl-N-(2,2,2-trichloro-1-(3-(4-fluoro-3-nitrophenyl)thioureido)ethyl)acetamideInChiKey:HLCDNLNLQNYZTK-UHFFFAOYSA-NInChiCode:InChI=1S/C23H18Cl3FN4O3S/c24-23(25,26)21(30-22(35)28-16-11-12-17(27)18(13-16)31(33)34)29-20(32)19(14-7-3-1-4-8-14)15-9-5-2-6-10-15/h1-13,19,21H,(H,29,32)(H2,28,30,35)SMILESCode:O=C(NC(NC(NC1=CC=C(F)C([N+]([O-])=O)=C1)=S)C(Cl)(Cl)Cl)C(C2=CC=CC=C2)C3=CC=CC=C3TechnicalDataAppearance:SolidpowderPurity:>98%(orrefertotheCertificateofAnalysis)ShippingCondition:Shippedunderambienttemperatureasnon-hazardouschemical.ThisproductisstableenoughforafewweeksduringordinaryshippingandtimespentinCustoms.StorageCondition:Dry,darkandat0-4Cforshortterm(daystoweeks)or-20Cforlongterm(monthstoyears).Solubility:SolubleinDMSO,notinwaterShelfLife:>2yearsifstoredproperlyDrugFormulation:ThisdrugmaybeformulatedinDMSOStockSolutionStorage:0-4Cforshortterm(daystoweeks),or-20Cforlongterm(months).HarmonizedSystemCode:293490AdditionalInformation  CGK733fraud(copiedfrom:http://en.wikipedia.org/wiki/CGK733_fraud)   CGK733wasasyntheticchemicalsubstancewhichwasreportedin2006tohaveremarkablepropertiesinreversingcellsenescence(aging). However,theentireworkbehindthediscoveryofthiscompoundhassincebeenfoundtobefalsifiedandtheauthorsoftheoriginalreportshaveretractedalltheirclaims. CGK733wasclaimedtobeaninhibitorofATM/ATRkinases, whichareinvolvedinDNAdamagerepair.CGKwasclaimedtoextendthelifetimeofculturedcellsbyapproximately20divisions,orroughly25%,specificallyinmammaliancells. Theoriginalreportgarneredscientificattention,butwasretractedin2008.TheretractionstatesthatthescreentoidentifyCGK733asananti-senescenceagentwasnotcarriedout;experimentsexploringthecellulareffectsofCGK733weremisrepresented;theidentificationofATMasthetargetofCGK733wasfabricated;acompoundwhichwasessentialforATMtargetvalidationhadnotbeensynthesized;andthechemicalstructureofCGK733wasmisrepresented.Theprincipalinvestigator,TaeKookKim,andseveralassociateswereconsequentlysUSPendedfromtheirpositionsattheKoreaAdvancedInstituteofScience&Technology.   References1:JekimovsC,BoldersonE,SuraweeraA,AdamsM,O'ByrneKJ,RichardDJ.ChemotherapeuticcompoundstargetingtheDNAdouble-strandbreakrepairpathways:thegood,thebad,andthepromising.FrontOncol.2014Apr22;4:86.doi:10.3389/fonc.2014.00086.eCollection2014.Review.PubMedPMID:24795863;PubMedCentralPMCID:PMC4001069.2:TangML,KhanMK,CroxfordJL,TanKW,AngeliV,GasserS.TheDNAdamageresponseinducesantigenpresentingcell-likefunctionsinfibroblasts.EurJImmunol.2014Apr;44(4):1108-18.doi:10.1002/eji.201343781.Epub2014Feb16.PubMedPMID:24375454.3:WilliamsTM,NyatiS,RossBD,RehemtullaA.MolecularimagingoftheATMkinaseactivity.IntJRADIatOncolBiolPhys.2013Aug1;86(5):969-77.doi:10.1016/j.ijrobp.2013.04.028.Epub2013May29.PubMedPMID:23726004;PubMedCentralPMCID:PMC3710537.4:FalloneF,BrittonS,NietoL,SallesB,MullerC.ATRcontrolscellularadaptationtohypoxiathroughpositiveregulationofhypoxia-inducIBLefactor1(HIF-1)expression.Oncogene.2013Sep12;32(37):4387-96.doi:10.1038/onc.2012.462.Epub2012Oct22.PubMedPMID:23085754.5:WangH,ZuoB,WangH,RenL,YangP,ZengM,DuanD,LiuC,LiM.CGK733enhancesmultinucleatedcellformationandcytotoxicityinducedbytaxolinChk1-deficientHBV-positivehepatocellularcarcinomacells.BiochemBiophysResCommun.2012May25;422(1):103-8.doi:10.1016/j.bbrc.2012.04.115.Epub2012Apr30.PubMedPMID:22564734.6:ChoiS,ToledoLI,Fernandez-CapetilloO,BakkeNISTCJ.CGK733doesnotinhibitATMorATRkinaseactivityinH460humanlungcancercells.DNARepair(Amst).2011Oct10;10(10):1000-1;authorreply1002.doi:10.1016/j.dnarep.2011.07.013.Epub2011Aug23.PubMedPMID:21865098;PubMedCentralPMCID:PMC3189494.7:TakahashiA,MoriE,SuX,NakagawaY,OkamotoN,UemuraH,KondoN,NodaT,TokiA,EjimaY,ChenDJ,OhnishiK,OhnishiT.ATMisthepredominantkinaseinvolvedinthephosphorylationofhistoneH2AXafterheating.JRadiatRes.2010;51(4):417-22.Epub2010Apr24.PubMedPMID:20448412.8:AlaoJP,SunnerhagenP.TheATMandATRinhibitorsCGK733andcaffeinesuppresscyclinD1levelsandinhibitcellproliferation.RadiatOncol.2009Nov10;4:51.doi:10.1186/1748-717X-4-51.PubMedPMID:19903334;PubMedCentralPMCID:PMC2777912.9:NormileD.Scientificmisconduct.Scienceretractsdiscreditedpaper;bitterpatentdisputecontinues.Science.2009Apr24;324(5926):450-1.doi:10.1126/science.324_450.PubMedPMID:19390012.10:CrescenziE,PalumboG,deBoerJ,BradyHJ.Ataxiatelangiectasiamutatedandp21CIP1modulatecellsurvivalofdrug-inducedsenescenttumorcells:implicationsforchemotherapy.ClinCancerRes.2008Mar15;14(6):1877-87.doi:10.1158/1078-0432.CCR-07-4298.PubMedPMID:18347191.
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(1)上市抗癌药库:该库将含有大约100个全球已批准上市的小分子抗癌化合物;
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(4)抗癌分子预制模块库:该库主要含有用于组建抗癌目标分子的分子模块包;
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