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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/Dorsomorphin dihydrochloride(Synonyms: BML-275 dihydrochloride; Compound C dihydrochloride)/HY-13418/10mM*1mL
商品详细Medchemexpress/Dorsomorphin dihydrochloride(Synonyms: BML-275 dihydrochloride; Compound C dihydrochloride)/HY-13418/10mM*1mL
Medchemexpress/Dorsomorphin dihydrochloride(Synonyms: BML-275 dihydrochloride; Compound C dihydrochloride)/HY-13418/10mM*1mL
Medchemexpress/Dorsomorphin dihydrochloride(Synonyms: BML-275 dihydrochloride; Compound C dihydrochloride)/HY-13418/10mM*1mL
商品编号： HY-13418-10mM*1mLinWater
品牌： MedChemExp
市场价： ¥1320.00
美元价： 792.00
产地： 美国(厂家直采)
公司：
产品分类： 小分子
公司分类： Small_molecule
联系Q Q： 3392242852
电话号码： 4000-520-616
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商品介绍
DorsomorphindihydrochlorideisapotentandselectiveAMPKinhibitor,thatiscompetitivewithATP,withKiof109±16nMintheabsenceofAMP.
Description

DorsomorphindihydrochlorideisapotentandselectiveAMPKinhibitor,thatiscompetitivewithATP,withKiof109±16nMintheabsenceofAMP.

IC50&Target

Ki:109±16nM(AMPK)[1]

InVitro

HT1080cellsaretreatedwith10μMDorsomorphinfor2hunder2DGstress.ImmunoblotanalysisrevealsthatphosphorylationlevelsofthecatalyticαsubunitofAMPKareincreasedbyexposureofHT1080cellsto2DG,whereasbothbasaland2DG-inducedphosphorylationlevelsareclearlyreducedwhenDorsomorphinisadded.MeasurementsofcellularkinaseactivityusinganELISA-basedassaysystemconfirmedthatDorsomorphindoesreducetheendogenousAMPKactivityregardlessofcellcultureconditions[2].

InVivo

AdmiNISTrationofDorsomorphinover24hleadstoa60%increaseintotalserumironconcentrations.Dorsomorphintreatmentisthereforeeffectiveinreducingbasallevelsofhepcidinexpressionandincreasingserumironconcentrationsinadultmice[3].

References

  • [1].ZhouG,etal.RoleofAMP-activatedproteinkinaseinmechanismofmetforminaction.JClinInvest.2001Oct;108(8):1167-74.

    [2].SaitoS,etal.CompoundCpreventstheunfoldedproteinresponseduringglucosedeprivationthroughamechanismindependentofAMPKandBMPsignaling.PLoSOne.2012;7(9):e45845.

    [3].YuPB,etal.DorsomorphininhibitsBMPsignalsrequiredforembryogenesisandironmetabolism.NatChemBiol.2008Jan;4(1):33-41.

    [4].ZhangDY,etal.Roleofautophagyanditsmolecularmechanismsinmiceintestinaltractaftersevereburn.JTraumaAcuteCareSurg.2017Oct;83(4):716-724.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.1168mL10.5840mL21.1681mL
5mM0.4234mL2.1168mL4.2336mL
10mM0.2117mL1.0584mL2.1168mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
KinaseAssay
[2]

HT1080cellsareseededin24-wellplates(2×104cellsperwell)andtreatedwithDorsomorphininthepresenceorabsenceofglucoseor10mM2DGfor2h.HT1080cellsthatoverexpressedthewild-typeanddominantnegativeAMPKα1arepreparedbytransfectingplasmidDNA(pAMPKα1-wt,pAMPKα1-D168AandpcFlagasacontrol)in6-wellplates,seedingin24-wellplateandtreatingwithUPRinhibitors.Cellsarelysedwithcelllysisbuffer(20mMTris-HCl,pH7.5,250mMNaCl,10%glycerol,0.5%NP-40,1mMEDTA,1mMEGTA,0.2mMPMSF,1μg/mLpepstatin,0.5μg/mLleupeptin,5mMNaF,2mMNa3Vo4,2mMβ-glycerophosphate,1mMDTT).RelativeAMPKkinaseactivity(mean±SDofduplicatedeterminations)tocontrolsample(vehicleorpcFlagundernormalgrowthconditions)isdeterminedusingtheCycLexAMPKkinaseassaykit[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

CellAssay
[2]

DorsomorphinisdissolvedinDMSO(10mM)andstored,andthendilutedwithappropriatemedia(DMSO0.5%)beforeuse[2].

HeLaand786-OcellsaretreatedwithvariousconcentrationsofDorsomorphin(0,0.3,1,3,10μM),VersipelostatinandPhenformininthepresenceorabsenceof10mM2DGor1μg/mLofTunicamycinasastressorfor30hin96-wellplates.Forthecombinationstudy,786-OcellsaretreatedwithvariousconcentrationsofUPRinhibitorsinthepresenceorabsenceof10mM2DGfor24h.Themediumisthenreplacedwithfreshgrowthmedium,andcellsareculturedforafurther15h.Subsequently,MTTisaddedtotheculturemedium,andtheabsorbanceofeachwellisdetermined.FortheviABIlityassayunderglucose-withdrawalconditions,HT1080cellsaretreatedwithvariousconcentrationsofDorsomorphinandphenforminin12-wellplatesinthepresenceorabsenceofglucosefor18h,seededin96-wellplateswithgrowthmedium,andthenculturedforafurther48hbeforeMTTisadded.Relativecellsurvival(mean±SDofquadruplicatedeterminations)iscalculatedbysettingeachcontrolabsorbancefromuntreatedcellsas100%.Theeffectsofdrugcombinationsatconcentrationsproducing80%cellgrowthinhibition(IC80)areanalyzedusingtheisobologrammethod[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[3]

DorsomorphinispreparedasastocksolutioninDMSO[3].

Mice[3]
12-week-oldC57BL/6miceraisedonastandarddietareinjectedviathetailveinwith0.2g/kgofDextranor0.2g/kgofiron-dextranUSP.Dextranisinjectedwithvehicleonly,whereasiron-dextranisinjectedwitheithervehicleorDorsomorphin(10mg/kg).1hafterinjection,micearekilledandliversegmentsarecollectedin500μLofSDS-lysisbufferandmechanicallyhomogenized.20μLofliverextractsareresolvedbySDS-PAGEandimmunoblotted.TotalRNAisharvestedusingTrizolfrommechanicallyhomogenizedmouselivers(6hafterinjectionwithasingleintraperitonealdoseofDorsomorphin(10mg/kg)orDMSO).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].ZhouG,etal.RoleofAMP-activatedproteinkinaseinmechanismofmetforminaction.JClinInvest.2001Oct;108(8):1167-74.

    [2].SaitoS,etal.CompoundCpreventstheunfoldedproteinresponseduringglucosedeprivationthroughamechanismindependentofAMPKandBMPsignaling.PLoSOne.2012;7(9):e45845.

    [3].YuPB,etal.DorsomorphininhibitsBMPsignalsrequiredforembryogenesisandironmetabolism.NatChemBiol.2008Jan;4(1):33-41.

    [4].ZhangDY,etal.Roleofautophagyanditsmolecularmechanismsinmiceintestinaltractaftersevereburn.JTraumaAcuteCareSurg.2017Oct;83(4):716-724.

MolecularWeight

472.41

Formula

C₂₄H₂₇Cl₂N₅O

CASNo.

1219168-18-9

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

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

H2O:≥48mg/mL;DMSO:5.2mg/mL(Needultrasonic)

Dorsomorphindihydrochlorideisdissolvedinsaline[4].

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

References

  • [1].ZhouG,etal.RoleofAMP-activatedproteinkinaseinmechanismofmetforminaction.JClinInvest.2001Oct;108(8):1167-74.

    [2].SaitoS,etal.CompoundCpreventstheunfoldedproteinresponseduringglucosedeprivationthroughamechanismindependentofAMPKandBMPsignaling.PLoSOne.2012;7(9):e45845.

    [3].YuPB,etal.DorsomorphininhibitsBMPsignalsrequiredforembryogenesisandironmetabolism.NatChemBiol.2008Jan;4(1):33-41.

    [4].ZhangDY,etal.Roleofautophagyanditsmolecularmechanismsinmiceintestinaltractaftersevereburn.JTraumaAcuteCareSurg.2017Oct;83(4):716-724.

Purity:99.73%