MELK-8a-hydrochloride-NVS-MELK8a-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMELK-8ahydrochlorideCat.No.:HY-100368ACASNo.:2096992-20-8Synonyms:NVS-MELK8ahydrochloride分⼦式:C₂₅H₃₃ClN₆O分⼦量:469.02作⽤靶点:MELK作⽤通路:PI3K/Akt/mTOR储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验H2O:≥100mg/mL(213.21mM)DMSO:8.6mg/mL(18.34mM;Needultrasonicandwarming)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1321mL10.6605mL21.3211mL5mM0.4264mL2.1321mL4.2642mL10mM0.2132mL1.0661mL2.1321mL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(sealedstorage,awayfrommoisture)。-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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：PBSSolubility:50mg/mL(106.61mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性MELK-8ahydrochloride⼀种新颖的母体胚胎亮氨酸拉链激酶（MELK）抑制剂，其IC50值为2nM。IC50&TargetIC50:2nM(MELK)[1]体外研究MELK-8aremainsverypotent(IC50=140nM)whentheATPconcentrationinthebiochemicalassayisshiftedfrom20μMto2mM.Itspotencyiswelltrackedbetweenfull-lengthMELKversuscatalyticdomainconstruct(5nMversus2nM).Itonlyinhibitssevenoff-targetkinasesinadditiontoMELKwith>85%inhibitionofbindingat1μMdemonstratinggreatselectivity.Thecompoundisatleast90-foldmoreselectiveintargetingMELKinallcases.MELK-8aisfairlysoluble(0.22g/LatpH6.8)andshowsagoodpermeabilityintheCaco-2assay.MELK-8ainhibitsthegrowthofMDA-MB-468cellsandMCF-7cellswithanIC50ofapproximately0.06and1.2μM,respectively[1].体内研究SubcutaneousadministrationofMELK-8aat30mg/kginC57BL/6miceresultsingoodplasmaexposure.Thecompoundadsorptionintothesystemiccirculationisrapid(Tmax=0.4h)andpeakplasmaconcentrationreaches6.6μM.AnascendingdosePKstudyinfemaleathymicnudemiceshowsthattherateofcompoundreleaseismaximalat120mg/kgandallclearancemechanismscanbesaturatedat240mg/kg.However,whenadministeredorallyat10mg/kginC57BL/6malemice,itshowsverypoorPK(3.6%oralbioavailability)consistentwithveryhighinvivoclearance[1].PROTOCOLCellAssay[1]MDA-MB-468andMCF7cellsareseededingrowthmediuminto96-wellplatesat1000and4000cells/well,respectively.Sixteenhoursafterplating,MELK-8aareaddedandincubatedfor7days.Foreachwell,ATPLitereagentisaddedandincubated.Luminescenceismeasuredonanmultilabelplatereader[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:Forpharmacokineticstudies,theintravenousandoraldoseispreparedinasolutioncontaining5%Administration[1]ethanol,100%PG,5%CremophorEL,and80%PBS.Thesubcutaneousdoseisformulatedin10%PGand25%(20%,v/v)Solutol.Plasmasamplesarecollectedatspecifiedtimepointsandstoredfrozen(−20°C)untilMELK-8aanalysis.AnLC−MS/MSmethodisusedtoquantitateMELK-8adruglevelsinplasma[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellRep.2017Dec5;21(10):2829-2841.•JBiolChem.2020Feb21;295(8):2359-2374.•SchoolofMedicine,DepartmentofPharmacology.2020Jun.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].TouréBB,etal.TowardtheValidationofMaternalEmbryonicLeucineZipperKinase:Discovery,OptimizationofHighlyPotentandSelectiveInhibitors,andPreliminaryBiologyInsight.JMedChem.2016May26;59(10):4711-23.McePdfHeight