LC Labs/P-8499 PD 184352, Free Base, >99%/P-8499/200 mg

• PD184352isaninhibitorofmitogenactivatedproteinkinasekinase(MEKorMAPKK).
• AntitumoractivityofPD184352isevidentinpreclinicalmodels,includingpancreas,colon,andbreastcancers,whichareassociatedwithitsinhibitionofpERK.Allen,L.F.,etal."CI-1040(PD184352),atargetedsignaltransductioninhibitorofMEK(MAPKK)."Semin.Oncol.30:105-116(2003).
• PD184352profoundlyinhibitedthegrowthof,andinducedapoptosisin,ovariantumorcellswithmutationsineitherKRASorBRAF.However,ovariancancercellscontainingwild-typesequenceswerenotsensitivetoPD184352.Pohl,G.,etal."Inactivationofthemitogen-activatedproteinkinasepathwayasapotentialtarget-basedtherapyinovarianSEROustumorswithKRASorBRAFmutations."CancerRes.65:1994-2000(2005).
• PD184352inhibitedC-RafwithanIC50of12nMandinhibitedmorethan90%ofERKphosphorylationataconcentrationof10nM.Invivo,PD184352decreasedadenomaformationandsignificantlyrestoredlungstructure.Kramer,B.W.,etal."UseofmitogeniccascadeblockersfortreatmentofC-Rafinducedlungadenomainvivo:CI-1040stronglyreducesgrowthandimproveslungstructure."BMCCancer4:24(2004).
• PD184352inhibitedtheMAPKpathwayandinducedapoptosisthroughapathwayinvolvedindephosphorylation,aggregationofFas-associateddeathdomainprotein,anddeathreceptor-independentcaspase-8activation.Meng,X.W.,etal."CentralRoleofFas-associatedDeathDomainProteininApoptosisInductionbytheMitogen-activatedProteinKinaseKinaseInhibitorCI-1040(PD184352)inAcuteLymphocyticLeukemiaCellsinVitro."J.Biol.Chem.278:47326-47339(2003).
• However,PD184352sufferedfrompoorpharmacokineticsbecauseofitslowsolubilityandrapidclearance.Barrett,S.D.,etal."ThediscoveryofthebenzhydroxamateMEKinhibitorsCI-1040andPD0325901."Bioorg.Med.Chem.Lett.18:6501-6504(2008).
• Soldforlaboratoryormanufacturingpurposesonly;notforhuman,medical,veterinary,food,orhouseholduse.
• ThisproductisofferedforR&Duseinaccordancewith(i)35USC271(e)+A13(1)intheU.S.;(ii)Section69.1ofJapanesePatentLawinJapan;(iii)Section11,No.2oftheGermanPatentActof1981inGermany;(iv)Section60,Paragraph5boftheU.K.PatentsActof1977intheU.K.;(v)Sections55.2(1)and55.2(6)andothercommonlawexemptionsofCanADIanpatentlaw;(vi)Section68BofthePatentsActof1953inNewZealandtogetherwiththeamendmentofsamebytheStatutesAmendmentBillof2002;(vii)suchrelatedlegislationand/orcaselawasmaybeorbecomeapplicableintheaforementionedcountries;and(viii)suchsimilarlawsandrulesasmayapplyinvariousothercountries.
• Notavailableinsomecountries;notavailabletosomeinstitutions;notavailableforsomeuses.

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Storage

Solubility

3mg/mLwithslightwarming;verypoorlysolubleinwater;maximumsolubilityinplainwaterisestimatedtobeabout5-10µMbuffers,serum,orotheradditivesmayincreaseordecreasetheaqueoussolu.Disposal