LY-364947-HTS466284-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemELY-364947Cat.No.:HY-13462CASNo.:396129-53-6Synonyms:HTS466284分?式:C??H??N?分?量:272.3作?靶點(diǎn):TGF-βReceptor作?通路:TGF-beta/Smad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:25mg/mL(91.81mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.6724mL18.3621mL36.7242mL5mM0.7345mL3.6724mL7.3448mL10mM0.3672mL1.8362mL3.6724mL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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/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:≥1.25mg/mL(4.59mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.25mg/mL(4.59mM);ClearsolutionBIOLOGICALACTIVITY?物活性LY-364947(HTS466284)?種有效的，ATP競(jìng)爭(zhēng)性的TGFβR-I抑制劑，IC50值為59nM，對(duì)TGFβR-II選擇性的7倍[1]。IC50&TargetIC50:59nM(TGFβR-I)體外研究LY-364947isanATPcompetitiveandtight-bindinginhibitor,inhibitingphosphorylationofP-Smad3byTGFβR-IKinasewithKiof28nM.LY-364947inhibitsinvivoSmad2phosphorylationwithintheNMuMgcellswithIC50of135nM.LY-364947reversesTGF-β-mediatedgrowthinhibitioninNMuMgcellswithIC50of0.218μM.LY-364947potentiatesthexVent2-luxBMP4responseinNMuMgcellsby30%atconcentrationsaslowas0.25μM.LY-364947(2μM)preventsTGF-β-inducedepithelial?mesenchymaltransitioninNMuMgcells[1].LY-364947(3μM)inducesexpressionofProx1andLYVE-1inalmostallHDLECsafter24hours[2].LY-364947promotesnuclearexportofFoxo3a,withlowSmad2/3andhighAktphosphorylationlevelsinleukaemia-initiatingcells.LY-364947([3].體內(nèi)研究LY-364947(1mg/kg,i.p.)accelerateslymphangiogenesis,asevidencebysignificantlyincreasingtheLYVE-1-positiveareasinamousemodelofchronicperitonitis.LY-364947(1mg/kg,i.p.)significantlyincreasestheLYVE-1-positiveareasintumortissuesintumorxenograftmodelsusingBxPC3pancreaticadenocarcinomacells[2].LY-364947(25mg/kg)increasesp-AktanddecreasesnuclearFoxo3ainleukaemia-initiatingcellsinCML-affectedmice[3].PROTOCOLAnimalBALB/cnudemice5to6weeksofageareusedintheassay.Parental,orVEGF-C-orTGF-β1-expressingAdministration[2]tumorcells(5×106)in100μLPBSareimplantedsubcutaneouslyintomalenudemiceandallowedtogrowfor2to3weekstoreachproliferativephase,beforeinitiationofTβR-Iinhibitoradministration.TβR-IinhibitorLY-364947,dissolvedin5mg/mLinDMSOanddilutedwith100μLPBS,orthevehiclecontrol,isinjectedintraperitoneallyat1mg/kg,3timesaweekfor3weeks.Excisedsamplesaredirectlyfrozenindry-icedacetoneforimmunohistochemistry.Frozensamplesarefurthersectionedat10-μmthicknessinacryostatandsubsequentlyincubatedwithprimaryandsecondaryantibodies.Samplesareobservedusingaconfocalmicroscope.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CellDiscov.2022Sep20;8(1):94.?PharmacolRes.2021Aug2;105797.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?CellBiosci.2019Jun14;9:48.?Oncogene.2019Jun;38(23):4637-4654.?Haematologica.2020Mar;105(3):674-686.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].PengSB,etal.KineticcharacterizationofnovelpyrazoleTGF-betareceptorIkinaseinhibitorsandtheirblockadeoftheepithelial-mesenchymaltransition.Biochemistry,2005,44(7),2293-2304.[2].OkaM,etal.InhibitionofendogenousTGF-betasignalingenhanceslymphangiogenesis.Blood,2008,111(9),4571-4579.[3].NakaK,etal.TGF-beta-FOXOsignallingmaintainsleukaemia-initiatingcellsinchronicmyeloidleukaemia.Nature,2010,463(7281),676-680.McePd