ALK-IN-26-DataSheet-生命科學(xué)試劑-MCE

Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEALK-IN-26Cat.No.:HY-156432CASNo.:2447607-85-2分子式:C??H??NO?S分子量:405.51作用靶點(diǎn):Anaplasticlymphomakinase(ALK);mTOR;PARP;Caspase作用通路:ProteinTyrosineKinase/RTK;PI3K/Akt/mTOR;CellCycle/DNADamage;Epigenetics;Apoptosis儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性ALK-IN-26(compound4a)是ALK抑制劑，對ALK酪氨酸激酶的IC50值為7.0μM。ALK-IN-26有良好的藥代動力學(xué)特性和血腦屏障通透性。ALK-IN-26能夠引起細(xì)胞凋亡、自噬和壞死。ALK-IN-26能夠用于膠質(zhì)母細(xì)胞瘤研究[1]。體外研究ALK-IN-26(0.5-2μM,24h)caninhibittheactivityofALKinGL216cells[1].ALK-IN-26(0.5-2μM,24h)canreducetheexpressionofmTORproteininGL216cells[1].[1].ALK-IN-26(0.5-2μM,24h)significantlydecreasesp-ERK1/2proteinlevelandenhancesp-JNKproteinlevelinGL261andU87MGcells,whilehaslittleeffectonp-AKTandp-STAT3proteinlevels[1].ALK-IN-26(0.5μM-2.0μM,24h)caninduceautophagyinGL261cells[1].ALK-IN-26(0.5μM-0.5μM,24-72h)increasestheproteinlevelsofcleaved-PARP(c-PARP)andcleaved-caspase-3(c-caspase3)inGL261cells[1].ALK-IN-26(0.5μM-2μM,24-72h)inducesapoptosisinGL261cells[1].ApoptosisAnalysis[1]CellLine:GL261Concentration:0.5μM,1.0μM,2.0μMIncubationTime:24h,48h,72hResult:Inducedapoptosisofglioblastomainaconcentration-andtime-dependentmanner,andcausedthecells(24.5%)enteredtheSphasebutbarelyproceededtotheG2/Mphase1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEwhentreatedwith1μMfor72h.CellViabilityAssay[1]CellLine:GL216,U87MG,HelaConcentration:0.5μM,1.0μM,2.0μM,5μM,10μMforGL216andU87MGcells5μM,10μM,20μM,40μM,80μM,160μMforHelacellsIncubationTime:24h,48h,72hResult:InhibitedtheactivityofGL216cellswiththeinhibitionrateofcellsat80%whenincubatedwith2μMfor72handinhibitedU87MGcellsviabilitywithadose-andtime-dependentmanner,whileshowedlimitedinhibitiononHelacells,evenat160μM,theinhibitionrateislessthan50%.CaninhibittheactivityofALKtyrosinekinasewithadose-dependentmanner.CellAutophagyAssay[1]CellLine:GL261Concentration:0.5μM,1.0μM,2.0μMIncubationTime:24hResult:Inducedautophagydeathinglioblastomacells.體內(nèi)研究ALK-IN-26(5mg/kg,i.v.,singledose)haspharmacokineticpropertiesinmaleC57BL6/Jmice[1].ALK-IN-26is(20mg/kg,i.p.,singledose)abletopenetratetheblood-brainbarrierinmaleC57BL6/Jmice[1].PharmacokineticparametersofC57BL6/Jinmalerats(n=3)[1]PharmacokineticpropertyT1/2(h)Tmax(h)Cmax(ng/mL)AUC(0-8)(h*ng/mL)AUC(0-∞)(h*ng/mL)MRT(0-8)(h)MRT(0-∞)(h)V∞(L/kg)V2(L/kg)bioavailablityF(%)i.v.(5mg/kg)1.130.081978.21884.88924.560.630.844.598.8938.40i.p.(5mg/kg)3.550.58117.57339.79420.502.254.60///AnimalModel:MaleC57BL/6Jmice[1]Dosage:5mg/kgAdministration:Intravenousinjection(i.v.),SingledoseResult:Couldberapidlyabsorbed(Tmax=0.58h)withanacceptablehalf-life(T1/2=3.55h)andbioavailability(F=38.4%).2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEAnimalModel:MaleC57BL/6Jmice[1]Dosage:20mg/kgAdministration:Intraperitonealinjection(i.p.),SingledoseResult:Couldenterthebodyatconcentrationsupto2.7μmol/kg(after2hadministrationat20mg/kg)andpenetratetheblood-brainbarrier.REFERENCESFengL,etal.SynthesisandBioevaluationof3-(Arylmethylene)indoleDerivatives:DiscoveryofaNovelALKModulatorwithAntiglioblastomaActivities[J].JournalofMedicinalChemistry,2023.McePdfHeightCaution:Producthas