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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/Talarozole(Synonyms: R115866)/HY-14531/10mM*1mL in DMSO
商品详细Medchemexpress/Talarozole(Synonyms: R115866)/HY-14531/10mM*1mL in DMSO
Medchemexpress/Talarozole(Synonyms: R115866)/HY-14531/10mM*1mL in DMSO
Medchemexpress/Talarozole(Synonyms: R115866)/HY-14531/10mM*1mL in DMSO
商品编号： HY-14531-10mM*1mLinDMSO
品牌： MedChemExp
市场价： ¥2800.00
美元价： 1680.00
产地： 美国(厂家直采)
公司：
产品分类： 小分子
公司分类： Small_molecule
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商品介绍
TalarozoleisapotentinhibitorofbothCYP26A1andCYP26B1,withIC50of0.46nMand5.1nMforCYP26B1andCYP26A1,respectively.

CustomerValidation

  • •JEnzymeInhibMedChem.2016;31(sup2):148-161.
  • •JCellPhysiol.2018Feb;233(2):1129-1145.
  • •MolPharmacol.2016May;89(5):560-74.
  • •MolPharmacol.2015;87(3):430-41.
  • •JExpZoolBMolDevEvol.2017Sep;328(6):575-586.
Description

TalarozoleisapotentinhibitorofbothCYP26A1andCYP26B1,withIC50of0.46nMand5.1nMforCYP26B1andCYP26A1,respectively.

IC50&Target

IC50:0.46/5.1nM(CYP26B1/A1)[1]

InVitro

WhenHepG2cellsarecotreatedwithatRAandTalarozole(1μM),4-OH-RAand4-oxo-RAformationissignificantlydecreased[2].

InVivo

Amaximum84%inhibitionofCYP26activityat0.5hourspost-doseispredictedbasedonTalarozole(TLZ)Cmaxof80nMandaKiof1nMfollowingasingledoseofTalarozole.DuetotheshortTalarozolehalf-life(2.2hrs)CYP26activityispredictedtoreturnto100%by12hours.Inagreementwiththepredictions,atRAconcentrationsareincreasedby82,63and60%at4hourspost-doseintheserum,liverandtestes,respectively,andconcentrationsreturnedtobaselineby24hours.FollowingmultipledosesofTalarozole,liverCYP26mRNAandactivityareincreasedsuggestingautoinductionofCYP26duetoincreasedatRAconcentrations.Inagreement,atRAconcentrationsareelevatedinserumandliveratalltimepointsmeasured.ThisincreaseinatRAconcentrationsisassociatedwithincreasedmRNAofthemitochondrialbiogenesisMarkersPGC-1βandNRF-1incomparisontocontrolmice[3].

References

  • [1].DiazP,etal.DevelopmentandCharacterizationofNovelandSelectiveInhibitorsofCytochromeP450CYP26A1,theHumanLiverRetinoicAcidHydroxylase.JMedChem.2016Mar24;59(6):2579-95.

    [2].TopletzAR,etal.InductionofCYP26A1bymetabolitesofretinoicacid:evidencethatCYP26A1isanimportantenzymeintheeliminationofactiveretinoids.MolPharmacol.2015;87(3):430-41.

    [3].FaithStevison,etal.CYP26InhibitionIncreasesRetinoicAcidConcentrationsinTargetTissuesandAltersRetinoidSignaling

    [4].TripathyS,etal.All-Trans-RetinoicAcidEnhancesMitochondrialFunctioninModelsofHumanLiver.MolPharmacol.2016May;89(5):560-74.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.6489mL13.2447mL26.4894mL
5mM0.5298mL2.6489mL5.2979mL
10mM0.2649mL1.3245mL2.6489mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
CellAssay
[2]

TalarozoleisdissolvedinDMSOandstored,andthendilutedwithappropriatemediumbeforeuse[2].

Humanlivermicrosomes(0.2mg/mL)areincubatedwith4-OH-atRA(500nM)andNADPH,NADP+orNAD+(eachat2mM)in100mMKPibufferpH7.4.Inaddition,4-OH-atRAisincubatedwithhumanlivermicrosomesinthepresenceandabsenceofTalarozole(1μM),aCYP26A1specificinhibitor,andKetoconazole(10μM)apan-P450inhibitorandwithNADPHasacofactor.Followinga5minpre-incubation,thereactionsareinitiatedwiththeadditionofcofactorandincubatedfor30minutes.At30minthereactionsarequenchedwithequalvolumeofAcetonitrileandcentrifugedat3,000gfor15min.Thesupernatantsarecollectedand4-oxo-atRAformationisanalyzedbyLC-MS/MS.Allincubationsarenormalizedtoanocofactorcontrol[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdmiNISTration
[3]

TalarozoleisdissolvedinDMSOandthendilutedwithPBSorsaline[3].

Mice[3]
Talarozoleisadministeredtomiceasasingledose(2.5mg/kg)orasmultipledosesforthreedays.SerumTalarozoleconcentrationsandserum,liverandtestesatRAconcentrationsaremeasuredbyLC-MS/MS.InhibitionofCYP26andchangesinatRAconcentrationsineachtissuearepredictedbasedonCYP26activityinvitroandTalarozoledisposition.MarkersoffattyacidoxidationintheliverandspermatogonialdifferentiationinthetestesaremeasuredfollowingTalarozoletreatment.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].DiazP,etal.DevelopmentandCharacterizationofNovelandSelectiveInhibitorsofCytochromeP450CYP26A1,theHumanLiverRetinoicAcidHydroxylase.JMedChem.2016Mar24;59(6):2579-95.

    [2].TopletzAR,etal.InductionofCYP26A1bymetabolitesofretinoicacid:evidencethatCYP26A1isanimportantenzymeintheeliminationofactiveretinoids.MolPharmacol.2015;87(3):430-41.

    [3].FaithStevison,etal.CYP26InhibitionIncreasesRetinoicAcidConcentrationsinTargetTissuesandAltersRetinoidSignaling

    [4].TripathyS,etal.All-Trans-RetinoicAcidEnhancesMitochondrialFunctioninModelsofHumanLiver.MolPharmacol.2016May;89(5):560-74.

MolecularWeight

377.51

Formula

C₂₁H₂₃N₅S

CASNo.

201410-53-9

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

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥36mg/mL

Talarozoleisdissolvedinpolyethyleneglycol300orvehiclecontrol[4].

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

References

  • [1].DiazP,etal.DevelopmentandCharacterizationofNovelandSelectiveInhibitorsofCytochromeP450CYP26A1,theHumanLiverRetinoicAcidHydroxylase.JMedChem.2016Mar24;59(6):2579-95.

    [2].TopletzAR,etal.InductionofCYP26A1bymetabolitesofretinoicacid:evidencethatCYP26A1isanimportantenzymeintheeliminationofactiveretinoids.MolPharmacol.2015;87(3):430-41.

    [3].FaithStevison,etal.CYP26InhibitionIncreasesRetinoicAcidConcentrationsinTargetTissuesandAltersRetinoidSignaling

    [4].TripathyS,etal.All-Trans-RetinoicAcidEnhancesMitochondrialFunctioninModelsofHumanLiver.MolPharmacol.2016May;89(5):560-74.

Purity:99.54%