LYN-1604-dihydrochloride-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemELYN-1604dihydrochlorideCat.No.:HY-101923BCASNo.:2310109-38-5分?式:C??H??Cl?N?O?分?量:657.54作?靶點:ULK;Autophagy;Apoptosis作?通路:Autophagy;Apoptosis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(76.04mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.5208mL7.6041mL15.2082mL5mM0.3042mL1.5208mL3.0416mL10mM0.1521mL0.7604mL1.5208mL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，并請注意儲備液的保存?式和期限。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，配制前請先配制澄的儲備液，再依次添加助溶劑(為保證實驗結(jié)果的可靠性，體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；澄的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分?指該溶劑在您配制終溶液中的體積占?)：1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(3.80mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(3.80mM);ClearsolutionBIOLOGICALACTIVITY1/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemE?物活性LYN-1604dihydrochloride?種有效的UNC-51樣激酶1(ULK1)激活劑，EC50值為18.94nM。LYN-1604可?于三性乳腺癌(TNBC)的研究[1]。IC50&TargetULK118.94nM(EC50)體外研究LYN-1604isapotentialULK1agonist(enzymaticactivity=195.7%at100nMandIC50=1.66μMagainstMDA-MB-231cells)[1].LYN-1604bindstowild-typeULK1withabindingaffinityinthenanomolerange(KD=291.4nM)[1].LYN-1604(0.5,1.0and2.0μM)inducescelldeathviatheULKcomplexinMDA-MB-231cells[1].LYN-1604(0.5-2μM,24hours)inducesremarkableup-regulationofBeclin-1anddegradationofp62,aswellastransformationofLC3-ItoLC3-IIinMDA-MB-231cells[1].LYN-1604inducesATG5-dependentautophagyviatheULKcomplex[1].LYN-1604canalsoincreasecleavageofcaspase3andinduceapoptosis[1].CellViabilityAssay[1]CellLine:MDA-MB-231cellsConcentration:0.5,1.0and2.0μMIncubationTime:Result:Inducedcelldeath.Autophagyratiowasincreasedinadose-dependentmanner.WesternBlotAnalysis[1]CellLine:MDA-MB-231cellsConcentration:0,0.5,1,and2μMIncubationTime:24hoursResult:Inducedremarkableup-regulationofBeclin-1anddegradationofp62,aswellastransformationofLC3-ItoLC3-II.體內(nèi)研究LYN-1604(lowdose,25mg/kg;mediandose,50mg/kg;highdose,100mg/kg;intragastricadministrationonceadayfor14days)inhibitsthegrowthofxenograftTNBCbytargetingULK1-modulatedcelldeath[1].AnimalModel:24femalenudemice(BALB/c,6-8weeks,20-22g)[1]Dosage:Lowdose,25mg/kg;mediandose,50mg/kg;highdose,100mg/kgAdministration:Intragastricadministration;onceadayfor14daysResult:SignificantlyinhibitedthegrowthofxenograftMDA-MB-231cells.Thebodyweightsofmicewerestable.Bytheendoftheexperiment,theliverandspleenweightindexesof2/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemEmicewereslightlyincreasedinpartsofthegroups,whilethekidneyweightindexwasnotaffectedinalldosegroups.?BiochemJ.2019Mar12;476(5):875-887.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ZhangL,etal.Discoveryofas