LC Labs/M-2900 Motesanib, Free Base, 99%/M-2900/25 mg

• Motesanib,alsoknownasAMG-706,isanorallyadmiNISTeredmultikinaseinhibitorthatselectivelytargetsVEGFreceptors,platelet-derivedgrowthfactorreceptors,andKitreceptorswithIC₅₀valuesof2nM(VEGFR1),3nM(VEGFR2),6nM(VEGFR3),84nM(PDGFR),and8nM(Kit).Itinhibitsangiogenesisandtumorgrowthintumorxenografts.Polverino, A.et al.,“AMG706,anoral,multikinaseinhibitorthatselectivelytargetsvascularendothelialgrowthfactor,platelet-derivedgrowthfactor,andkitreceptors,potentlyinhibitsangiogenesisandinducesregressionintumorxenografts.”Cancer Res. 66: 8715‑8721 (2006).
• HumanbreastcancerxenograftmodelswereestablishedinathymicnudemicebyimplantingMCF-7(luminal),MDA-MB-231(mesenchymal)tumorfragments,orCal-51(mixed/Progenitor)tumorcells.Motesanibtreatmentsignificantlyinhibitedthetumorgrowthdose-dependentlyandreducedviabletumorfractionandbloodvesseldensityinvivo.However,motesanibdidnotaffecttheproliferationoftumorcellsinvitro.Coxon, A.et al.,“Broadantitumoractivityinbreastcancerxenograftsbymotesanib,ahighlyselective,oralinhibitorofvascularendothelialgrowthfactor,platelet-derivedgrowthfactor,andKitreceptors.”Clin. Cancer Res. 15: 110‑118 (2009).
• MotesanibinhibitedmutatedKitkinaseautophosphorylation.Italsosuppressedkinasedomainmutationsconferringimatinibresistancebutdidnotinhibittheimatinib-resistantD816Vmutant.MotesanibinhibitedtheproliferationofBa/F3cellsexpressingKitmutants.Caenepeel, S.et al.,“MotesanibinhibitsKitmutationsassociatedwithgastrointestinalstromaltumors.”J. Exp. Clin. Cancer Res. 29: 96 (2010).
• MotesanibdemonstratedsomeantitumoractivityinaPhaseIstudy.Rosen, L.S.et al.,“Safety,pharmacokinetics,andefficacyofAMG706,anoralmultikinaseinhibitor,inpatientswithadvancedsolidtumors.”J. Clin. Oncol. 25: 2369‑2376 (2007).
• Motesanibinhibitedthyroidtumorxenograftgrowth,possIBLybyinhibitionofangiogenesisandexpressionofVEGFR2andRetontumorcells.Coxon, A.et al.,“AntitumorActivityofMotesanibinaMedullaryThyroidCancerModel.”J. Endocrinol. Invest. (Mar 21,2011-Epub ahead of print).
• InaphaseIIstudy,93patientswhohadprogressive,locallyadvancedormetastatic,rADIoiodine-resistantdifferentiatedthyroidcancerweretreatedwithmotesanibdiphosphate.Motesanibdiphosphateinducedpartialresponsesinthesepatients.Anticancerresponsesweredemonstratedin14%ofpatients.DiseasestABIlizationwasshownin67%ofpatients.Sherman, S.I.et al.,“Motesanibdiphosphateinprogressivedifferentiatedthyroidcancer.”N. Engl. J. Med. 359: 31‑42 (2008).
• AnotherCASnumberpreviouslyassignedtomotesanibfreebase,namely894356-47-9,hasbeendeletedbyCASandisnolongerinuse.
• 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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