Description | LY2835219aselectiveCDK4/6inhibitorwithIC50valuesof2nMand10nMforCDK4andCDK6,respectively. |
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IC50&Target | IC50:2nM(CDK4),10nM(CDK6)[3] |
InVitro | LY2835219reducescellviABIlitywiththeIC50valuesrangingfrom0.5μMto0.7μM,inhibitsAktandERKsignalingbutnotmTORactivationatheadandnecksquamouscellcarcinoma(HNSCC)cells[1].LY2835219showsinhibitiononA375R1-4,M14R,andSH4RwithEC50valuesrangingfrom0.3to0.6μM;LY2835219inhibitstheproliferationoftheparentalA375andresistantA375RV1andA375RV2cellswithsimilarpotencieswithIC50valuesof395,260,and463nM,respectively[2].LY2835219inhibitsCDK4andCDK6withlownanomolarpotency,inhibitsRbphosphorylationresultinginaG1arrestandinhibitionofproliferation,anditsactivityisspecificforRb-proficientcells[3]. |
InVivo | LY2835219(45mg/kg,p.o.)incombinationwitheverolimuscausesacooperativeantitumoreffectinHNSCCxenografttumor[1].LY2835219(45or90mg/kg,p.o.)showssignificanttumorgrowthinhibitioninanA375xenograftmodel[2]. |
References |
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KinaseAssay [1] | Cells(5×103)areplatedin96wellplates.Cellsaretreatedthenextdayfor24to48hoursandthenassessedforcaspase-3activitybyCaspase-Glo-3/7Assay,aspermanufacturer"sinstructionsandaluminescenceplatereader.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly. |
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CellAssay [1] | LY2835219isdissolvedinDMSOtoa10mMconcentration. Cellsareseededina96-wellplate,allowedtoadhereovernight,andtreatedwithDMSOcontrol(0.1%v/v)ortheindicatedcompoundsfor72h.CellviabilityandproliferationaredeterminedusingaCellCountingKitaccordingtothemanufacturer"sinstructions.TheinteractionbetweenLY2835219andmTORinhibitorisdeterminedusingCompuSyn.Combinationindex(CI)valuesof1indicatesandadditivedruginteraction,whereasaCIof<1=""is=""synergistic=""and=""a=""ci=""of="">1isantagoNISTic.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly. |
AnimalAdministration [1] | LY2835219isdissolvedin1%HECin20mMphosphatebuffer. Six-week-oldBALB/cfemalenudemiceareinjectedsubcutaneouslywithOSC-19(1×106)cells.Whentumorsizesreachapproximately100mm3,micearerandomizedbytumorsizeandsubjectedtoeachtreatment.Atleast5micepertreatmentgroupareincluded.Eachgroupofmiceisdosedviadailyoralgavagewithvehicle,LY2835219(45mg/kg/dor90mg/kg/d),Everolimus(5mg/kg/d),oracombinationofboth.TheLY2835219isdissolvedin1%HECin20mMphosphatebuffer(pH2.0).Tumorsizeandbodyweightaremeasuredtwiceweekly.Tumorvolumesarecalculatedusingthefollowingformula:V=(L×W2)/2(L,Length;W,width).Micearegavagedafinaltimeonday14andsacrificedthefollowingday.ThetumorsareremovedforWesternblotandimmunohistochemistry.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly. |
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MolecularWeight | 602.7 | ||||||||||||
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Formula | C₂₈H₃₆F₂N₈O₃S | ||||||||||||
CASNo. | 1231930-82-7 | ||||||||||||
Storage |
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Shipping | RoomtemperatureincontinentalUS;mayvaryelsewhere | ||||||||||||
Solvent&Solubility | H2O:≥250mg/mL LY2835219isdissolvedin1%HECin20mMphosphatebuffer(pH2.0)andadministeredorallybygavage(finalvolume0.2mL)[4]. *"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">1> | ||||||||||||
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Purity:99.87%
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