DI-591-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEDI-591Cat.No.:HY-124602CASNo.:2245887-38-9分?式:C??H??N?O?S分?量:585.8作?靶點(diǎn):E1/E2/E3Enzyme作?通路:MetabolicEnzyme/Protease儲存?式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:12.5mg/mL(21.34mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.7071mL8.5353mL17.0707mL5mM0.3414mL1.7071mL3.4141mL10mM0.1707mL0.8535mL1.7071mL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(fù)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(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?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(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.25mg/mL(2.13mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥1.25mg/mL(2.13mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.25mg/mL(2.13mM);ClearsolutionBIOLOGICALACTIVITY?物活性DI-591?種有效，?親和?和細(xì)胞滲透性的DCN1-UBC12相互作?的抑制劑。DI-591分別以Ki值為12nM和10.4nM與DCN1和DCN2結(jié)合，并且?乎不與DCN3，DCN4和DCN5蛋?結(jié)合。DI-591選擇性抑制cullin3的?烯化，但對其他cullin家族成員的?烯化沒有響或響很?。IC50&TargetDCN1-UBC12[1]體外研究DI-591(Compound44)bindstoDCN1andDCN2withKivaluesof12?nMand10.4nM,respectivelyandhasnoappreciablebindingtoDCN3,DCN4,andDCN5proteins.Hence,DI-591displaysavery-highbindingaffinitytorecombinanthumanDCN1andDCN2proteinsand>1000-foldselectivityoverrecombinanthumanDCN3-5proteins[1].DI-591(Compound44;0-10μM;1hour;KYSE70cells)bindstobothcellularDCN1andDCN2proteinsanddisruptstheassociationofcellularDCN1andUBC12proteins[1].DI-591(Compound44;10μM;24hours;THLE2cells)treatmentrobustlyincreasesthemRNAlevelsofNQO1andHO1,leadingtoupregulationofHO1proteininthecells.Significantly,DI-591hasnoeffectonthemRNAlevelofNRF2[1].Theselectiveinhibitionofneddylationofcullin3byDI-591leadstoaccumulationNRF2proteinanditstranscriptionalactivation.KnockdownexperimentsindicatethatDCN1,butnotDCN2,playsakeyroleinregulationofneddylationofcullin3butnotofothercullins.DI-591isanexcellentprobecompoundtoinvestigatetheroleofthecullin3CRL(Cullin-RINGE3ubiquitinligase)inbiologicalprocessesandhumandiseases[1].WesternBlotAnalysis[1]CellLine:KYSE70cellsConcentration:0μM,1μM,3Μmor10μMIncubationTime:1hourResult:PotentlyboundtocellularDCN1andDCN2proteins.EnhancedthestabilityofDCN1andDCN2proteininadose-dependentmanner.RT-PCR[1]CellLine:THLE2cellsConcentration:10μMIncubationTime:24hours2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:RobustlyincreasesthemRNAlevelsofNQO1andHO1.REFERENCES[1].ZhouH,etal.Apotentsmall-moleculeinhibitoroftheDCN1-UBC12interactionthatselectivelyblockscullin3neddylation.NatCommun.2017Oct27;8(1):1150.McePdfHeightCaution:Producthasnotbeenfullyval