请使用支持JavaScript的浏览器! Medchemexpress/Aloxistatin(Synonyms: E64d; E64c ethyl ester)/HY-100229/25mg_蚂蚁淘，【正品极速】生物医学科研用品轻松购|ebiomall 蚂蚁淘商城
欢迎来到蚂蚁淘！（生命科学科研用品平行进口B2B商城） 请登录 免费注册 询价篮
我的蚂蚁淘
产品分类
网站导航
微信关注
联系QQ
0
热门关键词 jackson二抗 Polyscience 23966 Liposomes脂质体 Biotium溴化乙锭 goldbio荧光素
我的购物车0
全部分类
酶
首页 品牌展示 产品查询 新闻资讯 帮助中心 联系我们 现货平台
商品信息
联系客服
Medchemexpress/Aloxistatin(Synonyms: E64d; E64c ethyl ester)/HY-100229/25mg
郑重提醒：
无质量问题不接受退换货，下单前请仔细核对信息。
下单后请及时联系客服核对商品价格，订单生效后再付款。
Medchemexpress/Aloxistatin(Synonyms: E64d; E64c ethyl ester)/HY-100229/25mg
品牌 / 
MedChemExpress
货号 / 
HY-100229-10mM*1mLinDMSO
官网地址
美元价：
(友情提示：该价格仅为参考，欢迎联系客服询价！)
数    量：
免费咨询热线
4000-520-616
商品介绍 售后保障 相关文章 商品咨询
联系客服
Aloxistatin(E64d)isabroad-spectrumcell-permeablecysteineproteaseinhibitor.
Description

Aloxistatin(E64d)isabroad-spectrumcell-permeablecysteineproteaseinhibitor.

IC50&Target

Cysteineprotease[1]

InVitro

Inhibitionofprotease-resistantprionprotein(PrP-res)accumulationinScNBcellsbycysteineproteaseinhibitorAloxistatin(E64d)withIC50of0.5±0.11μM.ForthecellsurfacePrP-sendetection,PrP-senisimmunoprecipitatedfrommediatreatedwithphosphatidylinositol-specificphospholipaseC(PIPLC)toreleasepulse-35S-labeledPrP-senfromthecellsurface.Aloxistatinismaintainedat15μM,respectively,inthelabelingmediaofallbutthecontrolcells[1].Aloxistatin(E64d)(whichspecificallyblockscysteineproteases,butnotserineproteasessuchasgranzymes)isabletocompletelyblockturnoveroftheCatLsubstrateZ-Phe-Arg-aminomethylcoumarin,whenpre-incubatedwithNK-92orYT5cells[2].Aloxistatin(E64d)isabroad-spectrumcell-permeableinhibitorofcysteineproteases[3].

InVivo

OraladmiNISTrationofAloxistatin(E64d)toguineapigsresultsinadose-dependentreductioninbrain,CSFandplasmaAβ(40)andAβ(42).Aloxistatinalsocausesabiphasicdose-dependentreductioninbrainCTFβ.Aloxistatincausesadose-dependentincreaseinbrainsAβPPα.ThemeansAβPPαlevelsaresignificantlyhigherthanthenodosegroupforAloxistatindosesof5mg/kg/dayorgreaterwiththehighestAloxistatindoseresultinginthemaximumincreaseinsAβPPαofabout54%morethanthecontrolgroup.SimilartotheAβeffect,oralAloxistatinadministrationproducesabiphasicdose-dependentreductioninbraincathepsinBactivity.Theminimumeffectivedoseisabout1mg/kg/daywiththehighestAloxistatindosecausingthemaximumreductioninbraincathepsinBactivityofabout91%lowerthanthatofthecontrolgroup.Thus,AloxistatinreducesguineapigbraincathepsinBactivityinamannerwhichisconsistentwiththecompoundinhibitingcathepsinBβ-secretaseactivity[4].Aloxistatin(E64d)inhibitstheincreasesintheexpressionofAT1ARandACEgenesinrats.AdministrationofOlmesartanorAloxistatinreducestheincreaseinthesuperoxideproductionoftheintramyocardialcoronaryarteriesinHFrats[5].

References

  • [1].Doh-UraK,etal.Lysosomotropicagentsandcysteineproteaseinhibitorsinhibitscrapie-associatedprionproteinaccumulation.JVirol.2000May;74(10):4894-7.

    [2].KonjarS,etal.HumanandmouseperforinareprocessedinpartthroughcleavagebythelysosomalcysteineproteinasecathepsinL.Immunology.2010Oct;131(2):257-67.

    [3].MullinsSR,etal.Three-dimensionalculturesmodelingpremalignantprogressionofhumanbreastepithelialcells:roleofcysteinecathepsins.BiolChem.2012Dec;393(12):1405-16.

    [4].HookG,etal.Thecysteineproteaseinhibitor,E64d,reducesbrainamyloid-βandimprovesmemorydeficitsinAlzheimer"sdiseaseanimalmodelsbyinhibitingcathepsinB,butnotBACE1,β-secretaseactivity.JAlzheimersDis.2011;26(2):387-408.

    [5].ChengXW,etal.Superoxide-dependentcathepsinactivationisassociatedwithhypertensivemyocardialremodelingandrepresentsatargetforangiotensinIItype1receptorblockertreatment.AmJPathol.2008Aug;173(2):358-69.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.9203mL14.6015mL29.2030mL
5mM0.5841mL2.9203mL5.8406mL
10mM0.2920mL1.4602mL2.9203mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
KinaseAssay
[2]

TheCTLsandNKcells(0.8×106/mL)aretreatedwiththeinhibitorsL1(10-20μM)orAloxistatin(20-30μM)for24hrat37°Cin24-wellplates.Cellsarethenusedin51Cr-releaseassaysorarelysedtoexamineperforininWesternblots.Theinhibitorisalsoaddedatthesameconcentrationduringthe4hrreactionsinsome51Cr-releaseassays,asindicated.CelllysatesarepreparedusingNP-40lysisbuffer(25mMHEPES,250mMNaCl,2.5mMethylenediaminetetraaceticacid,0.1%volume/volumeNonidetP-40)andtotalproteinconcentrationisdeterminedusingtheBradfordassay.Equalamountsofproteinareloadedandresolvedon8%SDS-PAGEgels.Humanormouseperforinisdetectedusingtheappropriateantibodiesasindicated.Anti-actinantibodyisusedasaloADIngcontrol[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

CellAssay
[3]

Aloxistatin(E64d)isdissolvedinDMSOandstored,andthendilutedwithappropriatemedium(finalDMSO0.1%)beforeuse[3].

CellproliferationandapoptosisareassessedbystainingforaproliferationMarker,Ki67,oranapoptoticmarker,cleavedcaspase3,followingtheprotocoldescribedaboveforthepolaritymarkers.MCF10variantsaregrownin3DrBMoverlayculturesfor4daysandaretreatedwith0.1%DMSO,5μMCA074Meor5μMAloxistatin.ThepercentageofstructuresthatarepositiveforKi67orcleavedcaspase3isdeterminedbycountingatotalof100structuresontwoseparatecoverslipswithaZeissAxiophotepifluorescentmicroscope.StructuresareconsideredKi67positiveiftheycontainedatleastonecellstainingforKi67.Structuresareconsideredtobecaspase3positiveiftheycontainedatleastonecellthatispositiveforcleavedcaspase3andthepositivecell(s)isnotlocalizedinthecenterofadevelopinglumen[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[4][5]

Aloxistatin(E64d)issUSPendedinMe2SO[4].

MiceandPig[4]
GuineaPigs(male,Hartleystrain,averageweight400gcorrespondingtoanimalsabout6weeksold)areused.MaletransgenicmiceexpressinghumanAβPPcontainingthewtβ-secretasesiteandtheLondonmutantβ-secretasesitesequencesareused.Deliveringadrugbygavageofferstheadvantageofaccuratedosingbutistraumaticandthusonlysuitableforrelativelyshortdosingperiods(uptoaboutaweek).Deliverybygavageisusedfortheguineapigstudies.AloxistatinissuspendedinMe2SOattheindicatedconcentrations(0.1,1.0,5,and10mg/kg)andadministeredbygavagedailyusingafeedingtube.VehiclecontrolanimalsaretreatedbygavageofMe2SOalone.
Rat[5]
MaleinbredDSratsareused.Weanedratsarefedlaboratorychowcontaining0.3%NaCluntil7weeksofage.DSratsfedan8%NaCldietafter7weeksmanifestcompensatedconcentricleftventricular(LV)hypertrophysecondarytohypertensionat12weeksandadistinctstageoffatalLVfailurewithlungcongestionat19weeks.DSratsarethereforefedan8%NaCldietfrom7weeksofageandarerandomizedtoanHFgroup,anAloxistatingroup(10mgperkgofbodymassperday,administeredintraperitoneallyeveryotherday),oranolmesartangroup(3mg/kgperdayinchow)from12to19weeksofage(n=10foreachgroup).Thedosesofolmesartan(anARB)andAloxistatinaredeterminedinpreliminaryexperimentsandpreviousstudies.DSratsmaintainedonthe0.3%NaCldietservedasage-matchedcontrols(controlgroup,n=10).At19weeksofage,alloftheratsareeuthanizedbyanintraperitonealoverdoseofsodiumpentobarbital(50mg/kg),andtheheartsareremovedforBIOLOGicalandhistologicalanalyses.ArterialbloodiscollectedfromtheaBDominalaortaforthemeasurementofreninactivity.Systolicbloodpressureandheartratearemeasuredinconsciousratsfrom7weeksofage,everyweek,usinganoninvasivetail-cuffmethod.Inseparateexperiments,12-week-oldDSrats,fedalow-saltdietfrom7weeksofage,aregivenvehicle,olmesartan,orAloxistatininthesamemannerasintheaboveexperiments(n=5foreachgroup),andtheLVtissuesformeasuringtargetingmRNAsandproteinlevelsareimmediatelyplacedinliquidnitrogenandstoredat-80°C.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].Doh-UraK,etal.Lysosomotropicagentsandcysteineproteaseinhibitorsinhibitscrapie-associatedprionproteinaccumulation.JVirol.2000May;74(10):4894-7.

    [2].KonjarS,etal.HumanandmouseperforinareprocessedinpartthroughcleavagebythelysosomalcysteineproteinasecathepsinL.Immunology.2010Oct;131(2):257-67.

    [3].MullinsSR,etal.Three-dimensionalculturesmodelingpremalignantprogressionofhumanbreastepithelialcells:roleofcysteinecathepsins.BiolChem.2012Dec;393(12):1405-16.

    [4].HookG,etal.Thecysteineproteaseinhibitor,E64d,reducesbrainamyloid-βandimprovesmemorydeficitsinAlzheimer"sdiseaseanimalmodelsbyinhibitingcathepsinB,butnotBACE1,β-secretaseactivity.JAlzheimersDis.2011;26(2):387-408.

    [5].ChengXW,etal.Superoxide-dependentcathepsinactivationisassociatedwithhypertensivemyocardialremodelingandrepresentsatargetforangiotensinIItype1receptorblockertreatment.AmJPathol.2008Aug;173(2):358-69.

MolecularWeight

342.43

Formula

C₁₇H₃₀N₂O₅

CASNo.

88321-09-9

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥23mg/mL

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

Purity:98.22%

匿名提交