Rheb-inhibitor-NR1-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERhebinhibitorNR1Cat.No.:HY-124798CASNo.:2216763-38-9分⼦式:C₂₅H₁₉BrCl₂N₂O₃S分⼦量:578.3作⽤靶点:mTOR作⽤通路:PI3K/Akt/mTOR储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(86.46mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.7292mL8.6460mL17.2921mL5mM0.3458mL1.7292mL3.4584mL10mM0.1729mL0.8646mL1.7292mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(4.32mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性RhebinhibitorNR1⼀种Rheb抑制剂，IC50为2.1μM。RhebinhibitorNR1可直接结合RhebswitchII结构域，选择性抑制mTORC1的激活。RhebinhibitorNR1抑制mTORC1驱动的T389pS6K1的磷酸化，并以剂量依赖的⽅式增加S473pAKT的磷酸化。RhebinhibitorNR1不响mTORC2的活性[1]。IC50&TargetRheb,mTORC1[1]体外研究NR1(1-10μM;48h)reducesthesizeofJurkatcells[1].NR1(0.37-30μM;90minforMCF-7andTRI102;24hforPC3)inhibitsthephosphorylationofT389pS6K1andincreasesthephosphorylationofS473pAKTinMCF-7,TRI102andPC3cells[1].NR1(1-30μM;2.5h)reducedproteinsynthesisinMCF-7[1].CellViabilityAssay[1]CellLine:JurkatcellsConcentration:1,3and10μMIncubationTime:48hResult:EffectivelyreducedthesizeofJurkatcellsinadose-dependentmanner.WesternBlotAnalysis[1]CellLine:MCF-7,TRI102andPC3cellsConcentration:0.37,1.1,3.3,10and30μMIncubationTime:90minforMCF-7andTRI102;24hforPC3Result:InhibitedthephosphorylationofT389pS6K1andincreasedthephosphorylationofS473pAKTinadose-dependentmanner.WesternBlotAnalysis[1]CellLine:MCF-7Concentration:1,3,10and30μMIncubationTime:2.5h(thenlabeledthecellswithan35S-Metlabelingmixfor30ꢀmin)Result:Dose-dependentlyreducedproteinsynthesis.体内研究NR1(30mg/kg;IP;singledosage)significantlyreducesmTORC1activityinbothkidneyandskeletalmuscle,andexhibitedaclearbandshiftforT37/464E-BP1inskeletalmuscle[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:MaleC57BL/6mice(6-7weeks;fastfor16hours)[1]Dosage:30mg/kgAdministration:IP;singledosageResult:Sustainedover5ꢀµMfor2ꢀh.SignificantlyreducedmTORC1activityinbothkidneyandskeletalmuscle,andexhibitedaclearbandshiftforT37/464E-BP1inskeletalmuscle.REFERENCES[1].MahoneySJ,etal.AsmallmoleculeinhibitorofRhebselectivelytargetsmTORC1signaling.NatCommun.2018Feb7;9(1):548.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedi