LC Labs/P-3333 PD 173074, Free Base, >99%/P-3333/50 mg

• PD173074selectivelyinhibitsthetyrosinekinaseactivitiesoftheFGFandVEGFreceptors.
• PD173074inhibitedthekinaseactivityofFGFR1withanIC50of25nMinvitro,whileinhibitingSrc,thereceptorsforinsulin,epidermalgrowthfactor(EGF)andPDGF,andseveralserine/threoninekinaseswith1000-foldorhigherIC50values.PD173074wasanATP-competitiveinhibitorofFGFR1,withaKiofaround40nM.PD173074inhibitedautophosphorylationofFGFR1andVEGFR2inadose-dependentmannerwithIC50sintherangeof1-5nMand100-200nM,respectively.MicetreateddailywithPD173074exhibiteddose-dependentinhibitionofFGF-inducedandVEGF-inducedneovascularization.However,PD173074wassomewhatlesseffectiveinblockingVEGF-inducedthanFGF-inducedangiogenesis.MohammADI,M.,etal."CrystalstructureofanangiogenesisinhibitorboundtotheFGFreceptortyrosinekinasedomain."EMBOJ.17:5896-5904(1998).
• PD173074inhibitedcellproliferationoftwolow-grade,noninvasivehumanbladderurothelialcarcinoma(UC)celllines,UM-UC-14andMGHU3,whichexpressedmutatedFGFR3protein.However,theothersixcelllinesexpressingwild-typeFGFR3orwithoutFGFR3expressionwereresistanttoPD173074treatment.Inthemousexenograftmodelssubcutaneouslytransplantedwiththesetwocelllines,orallyadmiNISTeredPD173074suppressedtumorgrowthandinducedapoptosis.Miyake,M.,etal."1-tert-butyl-3-[6-(3,5-dimethoxy-phenyl)-2-(4-diethylamino-butylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea(PD173074),aselectivetyrosinekinaseinhibitoroffibroblastgrowthfactorreceptor-3(FGFR3),inhibitscellproliferationofbladdercancercarryingtheFGFR3genemutationalongwithup-regulationofp27/Kip1andG1/G0arrest."J.Pharmacol.Exp.Ther.332:795-802(2010).
• TheFGFR1inhibitorPD173074dose-dependentlyinhibitedFGF-2promotionofgranuleneuronsurvivalunderlow-potassium,serum-freeconditionswithIC50of12nM,whenaddedtogetherwithFGF-2fora24-hpretreatmentpriortopotassiumwithdrawal.Skaper,S.D.,etal."TheFGFR1inhibitorPD173074selectivelyandpotentlyantagonizesFGF-2neurotrophicandneurotropiceffects."J.NeuRochem.75:1520-1527(2000).
• PD173074inhibitedtheproliferationandclonogenicgrowthofsmallcelllungcancercelllinesH-510andH-69invitroandinvivo.ItalsopreventedFGF-2-inducedchemoresistance.TheseeffectscorrelatedwiththeinhibitionofbothFGFR1andFGFR2transphosphorylation.Pardo,O.E.,etal."ThefibroblastgrowthfactorreceptorinhibitorPD173074blockssmallcelllungcancergrowthinvitroandinvivo."CancerRes.69:8645-8651(2009).
• PD173074inhibitedthegrowthofglioblastomacellsinvitro.Loilome,W.,etal."GlioblastomacellgrowthissuppressedbydisruptionofFibroblastGrowthFactorpathwaysignaling."J.Neurooncol.94:359-366(2009).
• Soldforlaboratoryormanufacturingpurposesonly;notforhuman,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.

Storage

Solubility

Disposal