RapaLink-1-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemERapaLink-1Cat.No.:HY-111373CASNo.:1887095-82-0分?式:C??H???N??O??分?量:1784.14作?靶點(diǎn):mTOR;Autophagy作?通路:PI3K/Akt/mTOR;Autophagy儲(chǔ)存?式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:178mg/mL(99.77mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM0.5605mL2.8025mL5.6049mL5mM0.1121mL0.5605mL1.1210mL10mM0.0560mL0.2802mL0.5605mL請(qǐng)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(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。BIOLOGICALACTIVITY?物活性RapaLink-1第三代mTOR抑制劑，通過(guò)linker將雷帕霉素(Rapamycin)與?代mTOR抑制劑MLN0128結(jié)合。RapaLink-1?雷帕霉素或mTOR抑制劑(TORKi)有更好的療效，能有效地阻斷癌性的，激活的mTOR突變體。RapaLink-1可以穿過(guò)?腦屏障。RapaLink-1與FKBP12的結(jié)合導(dǎo)致持久抑制mTORC1。RapaLink-1通過(guò)促進(jìn)?噬在抗磷脂綜合征中發(fā)揮抗?栓作?。具有抗癌活性。IC50&TargetmTOR體外研究RapaLink-1(0-200nM;3days)showsU87MGcellsgrowthinhibition[1].1/3MasterofSmallMolecules—您?邊的抑制劑?師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.體內(nèi)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?邊的抑制劑?師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