• Tipifarnib,alsoknownasR115777,isapotent,selective,non-peptideinhibitoroffarnesylproteintransferasethathassignificantantitumoreffectsinvivo.ItcompetitivelyinhibitedthefarnesylationoflaminB(IC50=0.86nM)andK-RasB(IC50=7.9nM)peptidesubstratesandinhibitedthecellgrowthof~75%ofapanelof53humantumorcelllinestested.TipifarnibproducedaprominentantiangiogenicresponseinLoVohumancolontumors,anantiproliferativeresponseinCAPAN-2humanpancreatictumors,andapoptosisinC32humanmelanoma.End,D.W.,etal."CharacterizationoftheAntitumorEffectsoftheSelectiveFarnesylProteinTransferaseInhibitorR115777inVivoandinVitro."CancerRes.61:131-137(2001).
• TipifarnibsignificantlyreduceddaunorubicineffluxinCCRF-CEMcells(IC50< 0.5 µM). It also inhibited cellular proliferation and induced apoptosis synergistically with daunorubicin. Tipifarnib has both P-glycoprotein inhibitory activity and farnesyl transferase inhibitory activity. Medeiros, B.C., et al. "The farnesyl transferase inhibitor, tipifarnib, is a potent inhibitor of the MDR1 gene product, P-glycoprotein, and demonstrates significant cytotoxic synergism against human leukemia cell lines." Leukemia 21: 739-746 (2007).
• Tipifarnibsignificantlydecreased(>85%)theproliferativeindexandincreasedapoptosisbyabout5-foldinallmammarycancerswithHaRasmutations,whereasvariableresponseswereobservedincancerswithoutHaRasmutations.Lubet,R.A.,etal."EffectsofthefarnesyltransferaseinhibitorR115777(Zarnestra)onmammarycarcinogenesis:prevention,therapy,androleofHaRasmutations."Mol.CancerTher.5:1073-1078(2006).
• Treatmentwithtipifarnibinhibitedcellgrowthinvitroandtumorgrowthinvivo,causedincreasedapoptosisanddecreasedproliferation,andreducedthecellturnoverindex.Wärnberg,F.,etal."Effectofafarnesyltransferaseinhibitor(R115777)onductalcarcinomainsituofthebreastinahumanxenograftmodelandonbreastandovariancancercellgrowthinvitroandinvivo."BreastCancerRes.8:R21-R30(2006).
• Tipifarnibblocksthegrowthofhumanpancreaticadenocarcinomacelllines;thisgrowthinhibitionisrelatedtoregulationintheextracellularsignal-regulatedkinases(ERK)andphosphorylationlevelsofsignaltransducerandactivatorsoftranscription3(STAT3).Venkatasubbarao,K.,etal."FarnesylTransferaseInhibitor(R115777)-InducedInhibitionofSTAT3(Tyr705)PhosphorylationinHumanPancreaticCancerCellLinesRequireExtracellularSignal-RegulatedKinases."CancerRes.65:2861-2871(2005).
• TipifarnibistheactiveingredientinthedrugsoldunderthetradenameZarnestra®.Thisdrugiscurrentlyapprovedinatleastonecountryforuseinelderlypatientswithnewlydiagnosedpoor-riskacutemyeloidleukemia.NOTE:THETIPIFARNIB,FREEBASERESEARCHCOMPOUNDSOLDBYLCLaboratoriesISNOTZARNESTRA®ANDISNOTFORHUMANUSE.
• Ourtipifarnibproductisthefreebase,whoseCASnumberisgivenabove.ChemicalAbstractsServicealsousesanotherCASnumberforthesamecompound,namely192185-68-5,buttheentryintheCASdatabasefor192185-68-5doesnotidentifythestereochemistry.
• 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.

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