KCN1,anovelsyntheticsulfonamide,isaHIFpathwayinhibitorwithpotentialanticanceractivityinvitroandinvivoanti-pancreaticcanceractivitiesandpreclinicalpharmacology.KCN1specificallyinhibitedHIFreportergeneactivityinseveralgliomacelllinesatthenanomolarlevel.KCN1alsodownregulatedtranscriptionofendogenousHIF-1targetgenes,suchasVEGF,Glut-1,andcarbonicanhydrase9,inahypoxia-responsiveelement(HRE)-dependentmanner.KCN1potentlyinhibitedthegrowthofsubcutaneousmalignantgliomatumorxenograftswithminimaladverseeffectsonthehost.MechaNISTically,KCN1didnotdownregulatethelevelsofHIF-1αorothercomponentsoftheHIFtranscriptionalcomplex;rather,itantagonizedhypoxia-inducIBLetranscriptionbydisruptingtheinteractionofHIF-1αwithtranscriptionalcoactivatorsp300/CBP.CONCLUSIONS:ThenewHIFpathwayinhibitorKCN1hasantitumoractivityinmousemodels,supportingitsfurthertranslationforthetreatmentofhumantumorsdisplayinghypoxiaorHIFoverexpression(source:ClinCancerRes.2012Nov21.[Epubaheadofprint])MedKooCat#:401515Name:KCN1CAS#:927823-01-6ChemicalFormula:C26H27NO5SExactMass:465.16099MolecularWeight:465.56ElementalAnalysis:C,67.08;H,5.85;N,3.01;O,17.18;S,6.89Synonym:KCN1;KCN-1;KCN1.IUPAC/ChemicalName:3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamideInChiKey:IPZJNJPAVPZHJM-UHFFFAOYSA-NInChiCode:InChI=1S/C26H27NO5S/c1-26(2)15-14-20-16-19(10-12-23(20)32-26)18-27(21-8-6-5-7-9-21)33(28,29)22-11-13-24(30-3)25(17-22)31-4/h5-17H,18H2,1-4H3SMILESCode:O=S(C1=CC=C(OC)C(OC)=C1)(N(CC2=CC(C=CC(C)(C)O3)=C3C=C2)C4=CC=CC=C4)=OTechnicalDataAppearance:SolidpowderPurity:>98%ShippingCondition:Shippedunderambienttemperatureasnon-hazardouschemical.ThisproductisstableenoughforafewweeksduringordinaryshippingandtimespentinCustoms.StorageCondition:Dry,darkandat0-4Cforshortterm(daystoweeks)or-20Cforlongterm(monthstoyears).Solubility:SolubleinDMSO,notinwaterShelfLife:>5yearsifstoredproperlyDrugFormulation:ThisdrugmaybeformulatedinDMSOStockSolutionStorage:0-4Cforshortterm(daystoweeks),or-20Cforlongterm(months).HarmonizedSystemCode:293490AdditionalInformation   ThefollowingdatawasfromPLoSOne.2012;7(9):e44883.doi:10.1371/journal.pone.0044883.Epub2012Sep13.       Figure1.InvitroanticanceractivitiesofKCN1againstpancreaticcancercells. (B)CellgrowthinhibitoryactivityofKCN1inhumanpancreaticcancercells.CellswereexposedtovariousconcentrationsofKCN1for72h,followedbyanMTTassay.(Source:PLoSOne.2012;7(9):e44883.doi:10.1371/journal.pone.0044883.Epub2012Sep13.)Figure1.InvitroanticanceractivitiesofKCN1againstpancreaticcancercells. (B)CellgrowthinhibitoryactivityofKCN1inhumanpancreaticcancercells.CellswereexposedtovariousconcentrationsofKCN1for72h,followedbyanMTTassay.()                References1:WangW,AoL,RayburnER,XuH,ZhangX,ZhangX,NagSA,WuX,WangMH,WangH,VanMeirEG,ZhangR.KCN1,anovelsyntheticsulfonamideanticanceragent:invitroandinvivoanti-pancreaticcanceractivitiesandpreclinicalpharmacology.PLoSOne.2012;7(9):e44883.doi:10.1371/journal.pone.0044883.Epub2012Sep13.PubMedPMID:23028659;PubMedCentralPMCID:PMC3441526.2:YinS,KaluzS,DeviNS,JabbarAA,deNoronhaRG,MunJ,ZhangZ,BoreddyPR,WangW,WangZ,AbbruscatoT,ChenZ,OlsonJJ,ZhangR,GoodmanMM,NicolaouKC,VanMeirEG.ArylsulfonamideKCN1InhibitsInVivoGliomaGrowthandInterfereswithHIFSignalingbyDisruptingHIF-1αInteractionwithCofactorsp300/CBP.ClinCancerRes.2012Nov21.[Epubaheadofprint]PubMedPMID:22923450;PubMedCentralPMCID:PMC3518680.