



下載本文檔
版權(quán)說(shuō)明:本文檔由用戶提供并上傳,收益歸屬內(nèi)容提供方,若內(nèi)容存在侵權(quán),請(qǐng)進(jìn)行舉報(bào)或認(rèn)領(lǐng)
文檔簡(jiǎn)介
Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETrametinib(DMSOsolvate)Cat.No.:HY-10999ACASNo.:1187431-43-1Synonyms:GSK-1120212(DMSOsolvate);JTP-74057(DMSOsolvate)分?式:C??H??FIN?O?S分?量:693.53作?靶點(diǎn):MEK;Apoptosis作?通路:MAPK/ERKPathway;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:69mg/mL(99.49mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.4419mL7.2095mL14.4190mL5mM0.2884mL1.4419mL2.8838mL10mM0.1442mL0.7209mL1.4419mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液;?旦配成溶液,請(qǐng)分裝保存,避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限:-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí),請(qǐng)?jiān)?個(gè)?內(nèi)使?,-20°C儲(chǔ)存時(shí),請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液,再依次添加助溶劑:(為保證實(shí)驗(yàn)結(jié)果的可靠性,澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件,適當(dāng)保存;體內(nèi)實(shí)驗(yàn)的?作液,建議您現(xiàn)?現(xiàn)配,當(dāng)天使?;以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?;如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象,可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑:10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(3.60mM);Clearsolution2.請(qǐng)依序添加每種溶劑:10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(3.60mM);Suspendedsolution;Needultrasonic3.請(qǐng)依序添加每種溶劑:10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(3.60mM);ClearsolutionBIOLOGICALACTIVITY?物活性Trametinib(DMSOsolvate)(GSK-1120212(DMSOsolvate);JTP-74057(DMSOsolvate))?服有效的MEK抑制劑,抑制MEK1和MEK2的IC50分別為2nM。Trametinib(DMSOsolvate)可以激活?噬(autophagy),誘導(dǎo)凋亡(apoptosis)。IC50&TargetMEK1MEK22nM(IC50)2nM(IC50)體外研究InBRAFmutantSK-MEL-28cellsandKRASmutantHCT116cells,Trametinib(GSK1120212;JTP-74057)DMSOsolvatecausesdose-dependentinhibitionofERK1/2phosphorylationaswellasdose-dependentgrowthinhibition.InbothSK-MEL-28andHCT116cells,TrametinibDMSOsolvateinhibits50%p-ERK1/2atnearlyequivalentconcentrations(0.8and1.8nM,respectively).However,astheslopesofthecurvesreflect,inSK-MEL-28cells,TrametinibDMSOsolvateinhibits90%p-ERK1/2atalowerconcentration(3.4nM)thaninHCT116(33.3nM).Furthermore,inbothcelllines,50%growthinhibitionisonlyachievedatconcentrationsTrametinibDMSOsolvatethatproducesnearcompleteERK1/2inhibition(85and90%,respectively)[2].體內(nèi)研究Trametinib(GSK1120212;JTP-74057)DMSOsolvateisevaluatedinvivoinanA549(KRASmutantcellline)xenograftmodel,orallydosingdailyfor21days(qd×21).Inthisstudy,nearcompletetumorgrowthinhibitionisobservedat5.0and2.5mg/kg[92and87%tumorgrowthinhibition(TGI),respectively]andtoalesserdegreeat0.5and0.1mg/kg(62and58%TGI).Although5mg/kgisthemaximallytolerateddose(MTD)inthisstudy,3mg/kgisthetypicallyobservedMTD.Dose-dependentantitumoractivitywithTrametinibDMSOsolvatetreatmenthasbeensimilarlyreportedforseveralotherKRASandBRAFmutanttumormodels[2].PROTOCOLCellAssay[2]SK-MEL-28,andHCT116celllinesareplatedintriplicate96wellmicrotitreplatesat5000cellsperwellinculturemedia.TrametinibdissolvedinDMSOornegativecontrol(0.1%DMSO)areaddedthefollowingdayandoneplateisharvestedwith50μLofCellTiter-Gloforatime0(T=0)measurement.Remainingduplicatecellplatesaretypicallyincubatedfor72h.Cellsarethenlysedwith50μLCellTiter-Glo,andchemiluminescentsignalisreadontheWallacEnVision2100platereader.FormeasurementofcellularERK1/2phosphorylation,cellsareseededandtreatedwithTrametinib,andlysedafter72hinTrislysisbuffersupplementedwithphosphataseandproteaseinhibitors.Allsamplesareanalyzedwithaphospho-ERK1/2ELISA.PlatesarereadonMSD.SI6000andcurvesareanalyzedusingtheXLfitcurve-fittingtool.ForcomparisonofthegrowthassaycurveandpERK1/2assaycurve,dataarebackgroundsubtractedand2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEnormalizedtothevehicletreatmentcontrol[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]A549(humannon-smallcelllungcarcinoma)modelisestablishedfromcellsgrownintissuecultureandharvestedasepticallyusingatrypsindigest.Femaleathymicmice(strainnu/nu)areinjectedsubcutaneouslywithbetween5×106and107cellsin50%martigel.Tumorsareallowedtoestablishforonetofourweeksbeforeuse.Trametinibisadministeredorallyattheindicateddosesin0.2mL/20gbyweight.TumorsaremeasuredtwiceweeklyusingVerniercalipers.Antitumoractivityisdefinedastumorgrowthinhibitionrepresentingthe%volumedifferentialintumorgrowthbetweenthetreatedandcontroltumorsatthetimevehicletumorsexceededavolumeof1000mm3.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Cell.2018Aug9;174(4):843-855.e19.?CancerCell.2021Aug9;39(8):1135-1149.e8.?CancerCell.2021May10;39(5):678-693.e11.?CancerCell.2020Mar16;37(3):387-402.e7.?CancerDiscov.2020Jun;10(6):872-887.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].YamaguchiT,etal.SuppressiveeffectofanorallyactiveMEK1/2inhibitorintwodifferentanimalmodelsforrheumatoidarthritis:acomparisonwithHWA486.InflammRes,2012,61(5),445-454.[2].AbeH,etal.DiscoveryofaHighlyPotentandSelectiveMEKInhibitor:GSK1120212(JTP
溫馨提示
- 1. 本站所有資源如無(wú)特殊說(shuō)明,都需要本地電腦安裝OFFICE2007和PDF閱讀器。圖紙軟件為CAD,CAXA,PROE,UG,SolidWorks等.壓縮文件請(qǐng)下載最新的WinRAR軟件解壓。
- 2. 本站的文檔不包含任何第三方提供的附件圖紙等,如果需要附件,請(qǐng)聯(lián)系上傳者。文件的所有權(quán)益歸上傳用戶所有。
- 3. 本站RAR壓縮包中若帶圖紙,網(wǎng)頁(yè)內(nèi)容里面會(huì)有圖紙預(yù)覽,若沒(méi)有圖紙預(yù)覽就沒(méi)有圖紙。
- 4. 未經(jīng)權(quán)益所有人同意不得將文件中的內(nèi)容挪作商業(yè)或盈利用途。
- 5. 人人文庫(kù)網(wǎng)僅提供信息存儲(chǔ)空間,僅對(duì)用戶上傳內(nèi)容的表現(xiàn)方式做保護(hù)處理,對(duì)用戶上傳分享的文檔內(nèi)容本身不做任何修改或編輯,并不能對(duì)任何下載內(nèi)容負(fù)責(zé)。
- 6. 下載文件中如有侵權(quán)或不適當(dāng)內(nèi)容,請(qǐng)與我們聯(lián)系,我們立即糾正。
- 7. 本站不保證下載資源的準(zhǔn)確性、安全性和完整性, 同時(shí)也不承擔(dān)用戶因使用這些下載資源對(duì)自己和他人造成任何形式的傷害或損失。
最新文檔
- 2025年T305型氧化鋅脫硫劑項(xiàng)目合作計(jì)劃書(shū)
- 2025年聲學(xué)懸浮物監(jiān)測(cè)儀項(xiàng)目建議書(shū)
- 2025年金屬制日用雜品合作協(xié)議書(shū)
- 專(zhuān)題05 有關(guān)金屬活動(dòng)性的探究-中考化學(xué)實(shí)驗(yàn)題型訓(xùn)練
- 勞務(wù)網(wǎng)簽合同范本
- 2025年橫包卷煙機(jī)組項(xiàng)目合作計(jì)劃書(shū)
- 農(nóng)村別墅設(shè)計(jì)裝修合同范例
- 銷(xiāo)售心態(tài)建設(shè)培訓(xùn)
- (高清版)DB5101∕T 81-2020 地理標(biāo)志產(chǎn)品 新民場(chǎng)生菜
- 費(fèi)用報(bào)銷(xiāo)付款流程
- 水電班組施工進(jìn)度計(jì)劃表
- 水土保持監(jiān)理實(shí)施細(xì)則
- 打印版80個(gè)常見(jiàn)象形字(一年級(jí)必備)課件
- 2024屆天津市天津一中高三第四次月考(英語(yǔ)試題文)試題含解析
- 醫(yī)院不良事件管理質(zhì)量評(píng)價(jià)標(biāo)準(zhǔn)
- 高中數(shù)學(xué)必修5《正弦定理與余弦定理》集體備課2課時(shí)表格式教案
- (現(xiàn)行版)江蘇省建筑與裝飾工程計(jì)價(jià)定額說(shuō)明及計(jì)算規(guī)則
- 重慶2023年重慶鈊渝金融租賃股份有限公司(籌)招聘上岸提分題庫(kù)3套【500題帶答案含詳解】
- JJG 596-1999電子式電能表
- GB/T 32854.4-2020自動(dòng)化系統(tǒng)與集成制造系統(tǒng)先進(jìn)控制與優(yōu)化軟件集成第4部分:信息交互和使用
- GB/T 21010-2017土地利用現(xiàn)狀分類(lèi)
評(píng)論
0/150
提交評(píng)論