Lonafarnib-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemELonafarnibCat.No.:HY-15136CASNo.:193275-84-2分⼦式:C₂₇H₃₁Br₂ClN₄O₂分⼦量:638.82作⽤靶点:FarnesylTransferase;Autophagy;InfluenzaVirus作⽤通路:MetabolicEnzyme/Protease;Autophagy;Anti-infection储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(78.27mM;Needultrasonic)扫描⼆维码，运⽤溶解⽅案计算器获得适合您实验体系的溶解⽅案MassSolvent1mg5mg10mgConcentration制备储备液1mM1.5654mL7.8269mL15.6539mL5mM0.3131mL1.5654mL3.1308mL10mM0.1565mL0.7827mL1.5654mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存⽅式和期限。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶1.请依序添加每种溶剂：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(3.91mM);Clearsolution此⽅案可获得≥2.5mg/mL(3.91mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述体系中加⼊50μLTween-80，混合均匀；然后继续加⼊450μL⽣理盐⽔定容⾄1mL。1/4www.MedChemEwww.MedChemE2.请依序添加每种溶剂：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(3.91mM);Clearsolution此⽅案可获得≥2.5mg/mL(3.91mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶3.液中，混合均匀。请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.5mg/mL(3.91mM);Clearsolution此⽅案可获得≥2.5mg/mL(3.91mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性Lonafarnib⼀种⼝服有效的法尼蛋⽩转移酶(FPTase)抑制剂，作⽤于H-ras，K-ras和N-ras，IC50分别为1.9nM，5.2nM和2.8nM。Lonafarnib具有抗肝炎三⾓洲病毒(HDV)的活性。IC50&TargetIC50:1.9nM(H-ras),5.2nM(K-ras),2.8nM(N-ras)[1]体外研究Lonafarnib(Sch66336)potentlyinhibitsHa-RasprocessinginwholecellsandblocksthetransformedgrowthpropertiesoffibroblastsandhumantumorcelllinesexpressingactivatedKi-Rasproteins[1].AlltreatmentgroupscontainingLonafarnib(10µM)showasignificantlyhigherlevelofunfarnesylatedH-Ras(116-137%)comparedtocontroltreatment[2].体内研究Inmouse,rat,andmonkeysystems,Lonafarnib(Sch66336)hasexcellentoralbioavailabilityandpharmacokineticproperties.Inthenudemouse,Lonafarnibdemonstratespotentoralactivityinawidearrayofhumantumorxenograftmodelsincludingtumorsofcolon,lung,pancreas,prostate,andurinarybladderorigin[1].Lonafarnibalone(80mg/kgbyoralgavage,oncedaily)haslimitedabilitytoinhibitorthotopicU87tumorscomparedtovehicletreatedcontrolanimals(T/Cof0.67).ThecombinationofXRT/Tem(2.5Gy/dayfor2days;5mg/kgbyoralgavage90minpriortoXRT)isdesignedtoproducemodesttumorgrowthinhibitioninvivo(T/Cof0.42).ConcurrentLonafarnib/XRT/Tem(Lonafarnib80mg/kgbyoralgavage,oncedaily,XRT2.5Gy/dayfor2days,andTem5mg/kgbyoralgavage90minpriortoXRT)providesthestrongestgrowthreduction(T/Cof0.02)andissignificantlymoreeffectivethanXRT/Tem(p<0.04),withthemajorityofanimalsdemonstratingadecreaseintumorvolume(p<0.05)aftertwoweeksandpersistingafter4weeks(p<0.05)[2].PROTOCOLKinaseAssay[1]FPTactivityisdeterminedbymeasuringthetransferof[3H]farnesylfrom[3H]farnesylPPitotrichloroaceticacid-precipitableHa-Ras-CVLS.GGPT-1activityissimilarlydeterminedusing[3H]geranylgeranyldiphosphateandHa-Ras-CVLLassubstrates[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[2]CellTiter96AqueousAssaykitisused.Assaysareperformedwith5000cells/wellina96-welltissueculture2/4www.MedChemEwww.MedChemEplate.Platesareirradiated24hafterdrugexposureandassayed96hafterXRT,withfreshdrugtreatmentsappliedeachday.Forquantification,dyeisaddeddirectlytoeachwell,platesarewashedasperthemanufacturesrecommendationandcellviabilitydeterminedbyopticaldensity.SignificanceisanalyzedusingtheStudent’sT-test.12-wellplatesareseededwith100,000cells/well.Drugtreatmentsareinitiated24hafterplating,andmediaisreplacedevery24hforatotalof96hofdrugexposure.Platesareirradiatedafter24hofdrugexposure.Cellsfromtriplicatesetsoftreatmentsaretrypsonizedandcounted48hafterirradationusingaZ1seriescoultercounter,andcomparedtocellnumbersfromwellscountedonDay1(thedaydrugtreatmentisinitiated).Proliferationafterdrugtreatmentsarenormalizedtothecontrolwellsandexpressedas%ofthecontroltreatment.SignificanceisanalyzedusingtheStudent’sT-test[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]Lonafarnibisgivenoncedailyat80mg/kgwithtwiceweeklyweightingstoensureaccuratedosing.Temozolomide(Tem)isgivenbygavageat5mg/kg90minpriortoXRT.Forirradiation,anesthetizedmiceareplacedinaleadshieldingapparatuswhichlimitedradiationexposuretotheheadonly.Treatment(2.5Gy/dayfortwodays)isdeliveredusingaGammacell40irradiatordelivering100rads/min.Forinvivocombinationexperiments,suboptimaldosesofXRT/TemareselectedtopermitidentificationofsynergisticeffectsofLonafarnib.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•NatCommun.2019May22;10(1):2265.•AgingCell.2019Aug;18(4):e12979.•SciRep.2019Jul10;9(1):10021.•MedMycol.2018Jun1;56(4):452-457.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LiuM,etal.AntitumoractivityofSCH66336,anorallybioavailabletricyclicinhibitoroffarnesylproteintransferase,inhumantumorxenograftmodelsandwap-rastransgenicmice.CancerRes.1998Nov1;58(21):4947-56.[2].ChaponisD,etal.Lonafarnib(SCH66336)impr