Dorsomorphin-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEDorsomorphinCat.No.:HY-13418ACASNo.:866405-64-3分?式:C??H??N?O分?量:399.49作?靶點:AMPK;TGF-βReceptor;Autophagy作?通路:Epigenetics;PI3K/Akt/mTOR;TGF-beta/Smad;Autophagy儲存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfromlight)溶解性數(shù)據(jù)體外實驗1MHCl:50mg/mL(125.16mM;ultrasonicandadjust掃描?維碼，pHto1withHCl)運?溶解?案計算器DMSO:5mg/mL(12.52mM;ultrasonicandwarming獲得適合您實驗體系的溶解?案andheatto80°C)H2O:3.33mg/mL(8.34mM;ultrasonicandadjustpHto6withHCl)Ethanol:3.33mg/mL(8.34mM;Needultrasonic)H2O:1mg/mL(2.50mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.5032mL12.5160mL25.0319mL5mM0.5006mL2.5032mL5.0064mL10mM0.2503mL1.2516mL2.5032mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存?式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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.請依序添加每種溶劑：0.5%CMC-Na/salinewater1/4www.MedChemEwww.MedChemE2.Solubility:26mg/mL(65.08mM);Suspendedsolution;Needultrasonic請依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥0.2mg/mL(0.50mM);Clearsolution此?案可獲得≥0.2mg/mL(0.50mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL2.0mg/mL的澄DMSO儲備液加到400μLPEG300中，混合均勻；向上述3.體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥0.2mg/mL(0.50mM);Clearsolution此?案可獲得≥0.2mg/mL(0.50mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL2.0mg/mL的澄DMSO儲備液加到900μL20%的SBE-β-CD?理鹽??溶4.液中，混合均勻。請依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥0.2mg/mL(0.50mM);Clearsolution此?案可獲得≥0.2mg/mL(0.50mM，飽和度未知)的澄溶液，此?案不適?于實驗周期在半個?以上的實驗。5.以1mL?作液為例，取100μL2.0mg/mL的澄DMSO儲備液加到900μL??油中，混合均勻。請依序添加每種溶劑：10%EtOH40%PEG3005%Tween-8045%salineSolubility:≥0.33mg/mL(0.83mM);Clearsolution此?案可獲得≥0.33mg/mL(0.83mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL3.3000002mg/mL的澄EtOH儲備液加到400μLPEG300中，混合均勻；向6.上述體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請依序添加每種溶劑：10%EtOH90%(20%SBE-β-CDinsaline)Solubility:≥0.33mg/mL(0.83mM);Clearsolution此?案可獲得≥0.33mg/mL(0.83mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL3.3000002mg/mL的澄EtOH儲備液加到900μL20%的SBE-β-CD?理鹽?7.?溶液中，混合均勻。請依序添加每種溶劑：10%EtOH90%cornoilSolubility:≥0.33mg/mL(0.83mM);Clearsolution此?案可獲得≥0.33mg/mL(0.83mM，飽和度未知)的澄溶液，此?案不適?于實驗周期在半個?以上的實驗。以1mL?作液為例，取100μL3.3000002mg/mL的澄EtOH儲備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性Dorsomorphin(CompoundC)?種選擇性，ATP競爭性的AMPK抑制劑(在沒有AMP的情況下，Ki為109nM)。Dorsomorphin選擇性抑制BMPI型受體ALK2，ALK3和ALK6。Dorsomorphin誘導(dǎo)?噬(autophagy)作?。IC50&TargetAMPKALK2ALK3ALK6109nM(Ki)Autophagy體外研究Dorsomorphin(compoundC)(0-10μM,18h)suppresses2DG-inducedGRP78promoteractivityinhumanfibrosarcomaHT1080cellsinadose-dependentmannerbuthaslittleeffectontunicamycin-inducedGRP782/4www.MedChemEwww.MedChemEpromoteractivity.Dorsomorphin(compoundC)CalsosuppressesGRP78promoteractivityinducedbyglucosewithdrawal.Dorsomorphin(compoundC)hasnoeffecton2DG-inducedPERKactivationandreducesthebothbasaland2DG-inducedAMPKphosphorylationlevelsinHT1080cells[2].WesternBlotAnalysis[2]CellLine:HumanfibrosarcomaHT1080cellsConcentration:0-10μM.IncubationTime:18hours.Result:Suppressed2DG-inducedGRP78promoteractivityinadose-dependentmannerandalsosuppressedGRP78promoteractivityinducedbyglucosewithdrawal.體內(nèi)研究Dorsomorphin(compoundC:10mg/kg,intravenouslyonce)treatmentleadstoa60%increaseintotalserumironconcentrations,reducesbasallevelsofhepcidinexpressionandincreasingserumironconcentrationsinadultmice[3].Dorsomorphin(compoundC:0.2mg/kg,I.V.,30minbeforeLPSinjection)reducesICAM-1andVCAM-1expressioninLPS-injectedrataorta[4].Dorsomorphin(compoundC;25mg/kg;i.p.injection;inmaleBALB/cmice)treatmentbeforelipopolysaccharide(LPS)injectionsignificantlyreduceslethalityincontrasttoanimalstreatedwithLPSchallengeonly[5].AnimalModel:Wild-type(WT)C57BL/6adultmicethatarefedastandardiron-repletedietexpresshighlevelsofhepcidin[3].Dosage:10mg/kg.Administration:Intravenouslyonce.Result:Ledtoa60%increaseintotalserumironconcentrations.Effectiveinreducingbasallevelsofhepcidinexpressionandincreasingserumironconcentrationsinadultmice.AnimalModel:MaleSprague-Dawleyrats,8weeksofage(bodyweight230-250g)[4].Dosage:0.2mg/kg.Administration:I.V.,30minbeforeLPSinjection.Result:ReducedICAM-1andVCAM-1expressioninLPS-injectedrataorta.AnimalModel:MaleBALB/cmiceat6-7weeksofageweighing20-22g[5]Dosage:25mg/kg3/4www.MedChemEwww.MedChemEAdministration:Injectioni.p.;60minbeforeLPSchallengeResult:Treatmentofmicewith25mg/kgbeforeLPSinjectionsignificantlyreducedlethalityincontrasttoanimalstreatedwithLPSchallengeonly.戶使?本產(chǎn)品發(fā)表的科研?獻?CellMetab.2021Mar2;33(3):565-580.e7.?MolCell.2020Jan2;77(1):95-107.e5.?MolCell.2017Oct19;68(2):336-349.e6.?RedoxBiol.2018Oct;19:339-353.?RedoxBiol.2018Jul;17:180-191.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ZhouG,etal.RoleofAMP-activatedproteinkinaseinmechanismofaction.JClinInvest.2001Oct;108(8):1167-74.[2].SaitoS,etal.CompoundCpreventstheunfoldedproteinresponseduringglucosedeprivationthroughamechanismindependentofAMPKandBMPsignaling.PLoSOne.2012;7(9):e45845.[3].YuPB,etal.DorsomorphininhibitsBMPsignalsrequiredforembryogenesisandironmetabolism.NatChemBiol.2008Jan;4(