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Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEEtomoxirCat.No.:HY-50202CASNo.:124083-20-1分⼦式:C₁₇H₂₃ClO₄分⼦量:326.82作⽤靶点:Apoptosis作⽤通路:Apoptosis储存⽅式:-20°C,protectfromlight,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(protectfromlight,storedundernitrogen)溶解性数据体外实验DMSO:140mg/mL(428.37mM;Needultrasonic)扫描⼆维码,H2O:<0.1mg/mL(insoluble)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1mM3.0598mL15.2989mL30.5979mL5mM0.6120mL3.0598mL6.1196mL10mM0.3060mL1.5299mL3.0598mL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(7.65mM);Clearsolution;Needultrasonic此⽅案可获得2.5mg/mL(7.65mM)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:3.5mg/mL(10.71mM);Suspendedsolution;Needultrasonic此⽅案可获得3.5mg/mL(10.71mM)的均匀悬浊液,悬浊液可⽤于⼝服和腹腔注射。以1mL⼯作液为例,取100μL35.0mg/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:≥3.5mg/mL(10.71mM);Clearsolution此⽅案可获得≥3.5mg/mL(10.71mM,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100μL35.0mg/mL的澄DMSO储备液加到900μL⽟⽶油中,混合均匀。BIOLOGICALACTIVITY⽣物活性Etomoxir((R)-(+)-Etomoxir)⾁碱棕榈酰转移酶1a(CPT-1a)抑制剂,通过抑制CPT-1a可抑制脂酸氧化,并抑制⼈、⼤⿏和豚⿏中棕榈酸酯的氧化。IC50&TargetCPT-1a[5]体外研究EtomoxirbindsirreversiblytothecatalyticsiteofCPT-1inhibitingitsactivity,butalsoupregulatesfattyacidoxidationenzymes.Etomoxirisdevelopedasaninhibitorofthemitochondrialcarnitinepalmitoyltransferase-1(CPT-1)locatedontheoutermitochondrialmembrane.Etomoxir,inthelivercanactasperoxisomalproliferator,increasingDNAsynthesisandlivergrowth.Thus,etomoxir,inadditionofbeingaCPT1inhibitorcouldbeconsideredasaPPARalphaagonist[1].EtomoxirisamemberoftheoxiranecarboxylicacidcarnitinepalmitoyltransferaseIinhibitorsandhasbeensuggestedasatherapeuticagentforthetreatmentofheartfailure.AcuteEtomoxirtreatmentirreversiblyinhibitstheactivityofcarnitinepalmitoyltransferaseI.Asaresult,fattyacidimportintothemitochondriaandβ-oxidationisreduced,whereascytosolicfattyacidaccumulatesandglucoseoxidationiselevated.Prolongedincubation(24h)withEtomoxirproducesdiverseeffectsontheexpressionofseveralmetabolicenzyme[2].体内研究Etomoxirisaninhibitoroffreefattyacid(FFA)oxidation-relatedkeyenzymeCPT1.P53interactsdirectlywithBax,whichisinhibitedbyEtomoxir,furtherconfirmingthedirectinteractionofP53andBax,andtheinvolvementofFAO-mediatedmitochondrialROSgenerationindb/dbmice[3].RatsareinjecteddailywithEtomoxir,aspecificCPT-Iinhibitor,for8daysat20mg/kgofbodymass.Etomoxir-treatedratsdisplaya44%reducedcardiacCPT-Iactivity.ThetreatmentofLewisratsfor8dayswith20mg/kgEtomoxirdoesnotalterbloodglucose,whichisinlinewithcomparableetomoxir-feedingstudies.Similarly,Etomoxirfeedingdoesnotaffectgeneralgrowthcharacteristicssuchasgaininbodymass,nordoesitaffecthindlimbmusclemass.However,heartmassandlivermassarebothsignificantlyincreasedby11%inEtomoxir-treatedrats[4].PROTOCOLCellAssay[2]RatheartH9c2myoblasticcellsareincubatedinDMEMcontaining10%fetalbovineserumuntilnearconfluence.Insomeexperiments,cellsarepreincubatedfor2hwithDMEM(serum-free)intheabsenceorpresenceof1-80μMEtomoxirandthenincubatedfor2hwith0.1mM[1-14C]oleicacid(10μCi/dish,bindsto2/4www.MedChemEwww.MedChemEBSAina1:1molarratio).Inotherexperiments,cellsarepreincubatedfor2hplusorminus40μMEtomoxirandthenincubatedfor2hwith0.1μMor0.1mM[1,3-3H]glycerol(10μCi/dish),0.1mM[1-14C]oleicacid(2μCi/dish,bindstoBSAina1:1molarratio),0.1mM[1-14C]palmiticacid(2μCi/dish,bindstoBSAina1:1molarratio),28μM[methyl-3H]choline(2μCi/dish),0.4mM[3H]serine(20μCi/dish),or40μMmyo-[3H]inositol(10μCi/dish).Themediumisremovedandthecellswashedtwicewithice-coldsalineandthenharvestedfromthedishwith2mLmethanol-water(1:1,v/v)forlipidextraction.Analiquotofthehomogenateistakenforthedeterminationoftotaluptakeofradioactivityintocells.Phospholipidsarethenisolatedandradioactivityinthesedetermined[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3][4]80maleC57BLKS/Jlar-Leprdb/dbmiceand20wildtypelittermates(8week)areused.db/dbmicearerandomlydividedintofourgroups:db/dbgroup,Etomoxirgroup,MitoQgroup,andPFT-αgroup.IntheEtomoxirgroup,miceareintraperitoneallyinjectedwith1mg/kgEtomoxirtwiceeveryweek.IntheMitoQgroup,50μMMitoQisgiventothemiceinwater.Waterbottles,containingeitherMitoQ,arecoveredwithaluminumfoil,andallbottlesarerefilledevery3days.InthePFT-αgroup,miceareintraperitoneallyinjectedwith1mg/kgPFT-αtwiceeveryweek.WTmiceareadministratedwithvehicleinstead.Theexperimentalperiodis8weeks.Attheend,peripheralbloodsamplesandbonemarrowcellsareharvestedfortheassays.Rats[4]MaleLewisrats,weighing150-200g,areusedinthepresentstudy.Animalsarekeptona12h:12hlight/darkcycleandfedaPurinaChowdietandwateradlibitum.Theratsaredividedintotwogroups:(1)controland(2)Etomoxir.Etomoxir(20mg/kgofbodyweight)isdissolvedin0.9%(w/v)NaClandadministeredintraperitoneallyfor8days.Controlratsreceivesaline.Thelastinjectionisgiven24hbeforetheexperiment.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•MolCell.2020Oct1;80(1):43-58.e7.•RedoxBiol.2018Oct;19:412-428.•RedoxBiol.2018Jul;17:180-191.•Theranostics.2020May16;10(14):6483-6499.•CellRep.2019Apr2;27(1):226-237.e4.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RuppH,etal.Theuseofpartialfattyacidoxidationinhibitorsformetabolictherapyofanginapectorisandheartfailure.Herz.2002Nov;27(7):621-36.[2].XuFY,etal.EtomoxirmediatesdifferentialmetabolicchannelingoffattyacidandglycerolprecursorsintocardiolipininH9c2cells.JLipidRes.2003Feb;44(2):415-23.[3].LiJ,etal.FFA-ROS-P53-mediatedmitochondrialapoptosiscontributestoreductionofosteoblastoge

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