Xcessbio/AZD6244 (Selumetinib), MEK Inhibitor -Xcessbio Biosciences Inc/50 mg solid/M60067-50s

AZD6244(Selumetinib,ARRY-142886)isanorallyactive,highlypotentandselectivenon-ATPcompetitiveMEKinhibitor,inhibitingMEK1withanIC₅₀of14nM.InvitrocellviABIlityinhibitionscreeningofatumorcelllinepanelfoundthatcelllinesharboringBRAForRASmutationsweremorelikelytobesensitivetoAZD6244.TreatmentofprimaryHCCcellswithAZD6244ledtogrowthinhibition,caspase-3andcaspase-7activation,poly(ADP)ribosepolymerasecleavage,andinhibitionofERK1/2andp90RSKphosphorylation.AZD6244significantlyinhibitsphosphorylationofERK1/2in2-1318,5-1318,26-1004and4-1318xenograftsandinducesapoptosisinprimary2-1318cellsbyactivatingthecaspasepathway.CurrentlyAZD6244isundergoingPhaseII/IIIclinicaltrialstotreatsolidtumors.

HowtoUse:

Invitro:AZD6244wasusedat5-10µMfinalconcentrationinvitroandincellularassays.

Invivo:AZD6244wasorallydosedtomiceat25-100mg/kgonceperday,orincombinationwithDocetaxel(15mg/kg)orIrinotecan(25mg/kg)tosignificantlyreducethetumorvolume.

Reference:

• 1.YehTC,etal.BiologicalcharacterizationofARRY-142886(AZD6244),apotent,highlyselectivemitogen-activatedproteinkinasekinase1/2inhibitor.(2007)ClinCancerRes.13(5):1576-83.
• 2.DaviesBR,etal.AZD6244(ARRY-142886),apotentinhibitorofmitogen-activatedproteinkinase/extracellularsignal-regulatedkinasekinase1/2kinases:mechanismofactioninvivo,pharmacokinetic/pharmacodynamicrelationship,andpotentialforcombinationinpreclinicalmodels.(2007)MolCancerTher.6(8):2209-19.
• 3.DryJR,etal.TranscriptionalpathwaysignaturespredictMEKaddictionandresponsetoselumetinib(AZD6244).(2010)CancerRes.70(6):2264-73.
• 4.BhallaS,etal.Thenovelanti-MEKsmallmoleculeAZD6244inducesBIM-dependentandAKT-independentapoptosisindiffuselargeB-celllymphoma.(2011)Blood.118(4):1052-61.
• 5.MorelliMP,etal.Preclinicalactivityoftherationalcombinationofselumetinib(AZD6244)incombinationwithvorinostatinKRAS-mutantcolorectalcancermodels.(2012)ClinCancerRes.18(4):1051-62.

AZD6244_spec.pdf

AZD6244_MSDS.pdf

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