RapaLink-1-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemERapaLink-1Cat.No.:HY-111373CASNo.:1887095-82-0分⼦式:C₉₁H₁₃₈N₁₂O₂₄分⼦量:1784.14作⽤靶点:mTOR;Autophagy作⽤通路:PI3K/Akt/mTOR;Autophagy储存⽅式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:178mg/mL(99.77mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制备储备液1mM0.5605mL2.8025mL5.6049mL5mM0.1121mL0.5605mL1.1210mL10mM0.0560mL0.2802mL0.5605mL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，并请注意储备液的保存⽅式和期限。BIOLOGICALACTIVITY⽣物活性RapaLink-1第三代mTOR抑制剂，通过linker将雷帕霉素(Rapamycin)与⼆代mTOR抑制剂MLN0128结合。RapaLink-1⽐雷帕霉素或mTOR抑制剂(TORKi)有更好的疗效，能有效地阻断癌性的，激活的mTOR突变体。RapaLink-1可以穿过⾎脑屏障。RapaLink-1与FKBP12的结合导致持久抑制mTORC1。RapaLink-1通过促进⾃噬在抗磷脂综合征中发挥抗⾎栓作⽤。具有抗癌活性。IC50&TargetmTOR体外研究RapaLink-1(0-200nM;3days)showsU87MGcellsgrowthinhibition[1].1/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemERapaLink-1(0-12.5nM;48hours)arrestsU87MGcellsatG0/G1[1].RapaLink-1selectivelyinhibitsp-RPS6S235/236andp-4EBP1T37/46atdosesaslowas1.56nM[1].Rapalink-1(100nM;24to96hours)suppressedrenalcellcarcinoma(RCC)cellproliferationbyinducingapoptosisandcellcyclearrest[2].RapaLink-1exploitstheuniquejuxtapositionoftwodrug-bindingpocketstocreateabivalentinteraction.RapaLink-1overcomesresistancetoexistingfirst-andsecond-generationinhibitors[3].CellProliferationAssay[1]CellLine:U87MGcellsConcentration:0-200nMIncubationTime:3daysResult:Showedgrowthinhibition.CellCycleAnalysis[1]CellLine:U87MGcellsConcentration:0-12.5nMIncubationTime:48hoursResult:ArrestedcellsatG0/G1.WesternBlotAnalysis[1]CellLine:U87MGcellsConcentration:0.39-12.5nMIncubationTime:3hoursResult:Selectivelyinhibitedp-RPS6S235/236andp-4EBP1T37/46atdosesaslowas1.56nM.ThemTORC2targetsp-AKTS473,p-SGK1S78,andp-NDRG1T346,andthep-AKTS473targetp-GSK3βS9wasinhibitedonlyathighdoses.体内研究RapaLink-1(i.p.;every5daysfor25days,thenonceaweekfor11week)showspotentanti-tumorefficacy[1].AnimalModel:BALB/Cnu/numicebearingU87MGintracranialxenografts[1]Dosage:1.5mg/kgAdministration:I.p.;every5daysfor25days,thenonceaweekfor11weekResult:Ledtoinitialregressionandsubsequentstabilizationoftumorsize.2/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].FanQ,etal.AKinaseInhibitorTargetedtomTORC1DrivesRegressioninGlioblastoma.CancerCell.2017Mar13;31(3):424-435.[2].KuroshimaK,etal.PotentialnewtherapyofRapalink-1,anewgenerationmammaliantargetofrapamycininhibitor,againstSU11248-resistantrenalcellcarcinoma.CancerSci.2020May;111(5):1607-1618.[3].MuF,etal.RapaLink-1playsanantithromboticroleinantiphospholipidsyndromebyimprovingautophagybothinvivoandvitro.BiochemBiophysResCommun.2020Apr30;525(2):384-391.[4].Rodrik-OutmezguineVS,etal.OvercomingmTORresistancemutationswithanew-generationmTORinhibitor.Nature.2016Jun9;534(7606):272-6.McePdfHeightCaution:Producthasnotbeenfullyvali