NAV-2729-DataSheet-生命科學試劑-MedChemExpressVIP

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemENAV-2729Cat.No.:HY-112473CASNo.:419547-11-8分?式:C??H??ClN?O?分?量:456.88作?靶點:Others作?通路:Others儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:50mg/mL(109.44mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1888mL10.9438mL21.8876mL5mM0.4378mL2.1888mL4.3775mL10mM0.2189mL1.0944mL2.1888mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(4.55mM);Suspendedsolution;Needultrasonic1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性NAV-2729?種Arf1/Arf6活化抑制劑。IC50&TargetArf6[1][2]Arf1[2]體外研究NAV-2729directlybindstoArf6.BasedonastructuralhomologymodeloftheArf6/Arf6-GEFcomplex,itispredictedthatNAV-2729associateswithArf6attheArf6GEF-bindingarea,whichisdistinctfromtheguaninenucleotide-bindingpocketofArf6.NAV-2729blocksARNO-andGEP100-mediatedguaninenucleotideexchangeonArf6.ThetreatmentofuvealmelanomacellswithNAV-2729interfereswithanchorage-independentgrowthofthecell[1].NAV-2729isadualArf1/Arf6inhibitorandismoreeffectivetowardArf1thanArf6.NAV-2729blocksspontaneousactivationofArf6anditsactivationbycytohesinsandBRAG.NAV-2729isaninhibitorofthespontaneousactivationofArf6,anditalsoinhibitstheactivationofArf6byitsGEFs,ARNOandBRAG2,insolution.TheinhibitoryprofileofNAV-2729isanalyzedataconcentrationof25μM,whichisreportedtoresultinalmosttotalinhibitionofspontaneousandGEF-stimulatedArf6activationinvitro.Undertheconditionsusedinassays,NAV-2729inhibitsspontaneousnucleotideexchangeofΔ13Arf6by~15%.NAV-2729inhibitstheactivationofΔ13Arf6byBRAG2Sec7PHby25%.Δ17Arf1hasnomeasurablespontaneousnucleotideexchange.ActivationofΔ17Arf1byBRAG2Sec7PHisinhibitedbyNAV-2729,andtheefficiencyismarkedlyhigherthanthatforArf6(50%).Inadose-responseexperiment,nucleotideexchangeratesarereducedby50%by10μMNAV-2729forΔ17Arf1while50%inhibitionisnotachievedevenat25μMNAV-2729forΔ13Arf6[2].體內(nèi)研究SystemictreatmentofmicewithNAV-2729interferewithtumorigenesisandtumorgrowthinorthotopicxenograftmousemodelofuvealmelanoma[1].REFERENCES[1].YamauchiY,etal.MachineriesregulatingtheactivityofthesmallGTPaseArf6incancercellsarepotentialtargetsfordevelopinginnovativeanti-cancerdrugs.AdvBiolRegul.2017Jan;63:115-121.[2].BenabdiS,etal.Family-wideAnalysisoftheInhibitionofArfGuanineNucleotideExchangeFactorswithSmallMolecules:EvidenceofUniqueInhibitoryProfiles.Biochemistry.2017Sep26;56(38):5125-5133.McePdfHeightCaution:Producthasnotbeenfullyvalidat