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Medchemexpress/Pioglitazone hydrochloride(Synonyms: U 72107A; AD 4833)/HY-14601/500mg
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Medchemexpress/Pioglitazone hydrochloride(Synonyms: U 72107A; AD 4833)/HY-14601/500mg
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4000-520-616
PioglitazonehydrochlorideisapotentandselectivePPARγagoNISTwithhighaffinitybindingtothePPARγligand-bindingdomainwithEC50of0.93and0.99μMforhumanandmousePPARγ,respectively.
Description

PioglitazonehydrochlorideisapotentandselectivePPARγagonistwithhighaffinitybindingtothePPARγligand-bindingdomainwithEC50of0.93and0.99μMforhumanandmousePPARγ,respectively.

IC50&Target

EC50:0.93μM(humanPPARγ),0.99μM(mousePPARγ)[1]

InVitro

AGEs-inducedbetacellnecrosisiscompletelyabrogatedbyaddingPioglitazonetotheAGEsculturemedium.FurThermorePioglitazonecompletelypreventedanyAGEs-inducedincrementincaspase-3activation,therebyrestoringcaspase-3activitytothesamelevelsasthecontrolcells.AsexpectedAGisabletocounteractAGEs-inducedimpairedviABIlity[2].

InVivo

Theserum-freefattyacidandtriglyceridelevelsaswellasADIpocytesizesinob/obandadipo-/-ob/obmiceareunchangedafter10mg/kgPioglitazonebutaresignificantlyreducedtoasimilardegreeafter30mg/kgPioglitazone.Moreover,theexpressionsofTNFαandresistininadiposetissuesofob/obandadipo-/-ob/obmiceareunchangedafter10mg/kgPioglitazonebutaredecreasedafter30mg/kgPioglitazone.Thus,Pioglitazone-inducedameliorationofinsulinresistanceanddiabetesmayoccuradiponectindependentlyintheliverandadiponectinindependentlyinskeletalmuscle[3].Pioglitazone(10mg/kgperd)treatmentsignificantlyattenuatesthelossofbodyweight(BW)andcardiachypertrophy.Pioglitazonetreatmentsignificantlyreducestheelevatedserumglucoselevelsandmarkedlyimprovedtheassociateddyslipidemia.Furthermore,thereisaslightbutsignificantincreaseinserumcreatininelevelinDratsovertheirNcontrols(P<0.05). however,="" a="" marked="" renal="" dysfunction="" is="" observed="" in="" diabetic="" nephropathic="" (dn)="" group=""><0.05). moreover,="" dn="" rats="" exhibits="" the="" highest="" serum="" activity="" of="" ck-mb,="" relative="" to="" both="" n="" and="" d="" rats=""><0.05). pioglitazone="" is="" able="" to="" decrease="" the="" elevated="" serum="" levels="" of="" both="" creatinine="" and="" creatine="" kinase-mb="">[4].

References
  • [1].KuwabaraK,etal.Anovelselectiveperoxisomeproliferator-activatedreceptoralphaagonist,2-methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxane-r-2-carboxylicacid(NS-220),potentlydecreasesplasmatriglycerideandglucoseleve

    [2].PudduA,etal.Pioglitazoneattenuatesthedetrimentaleffectsofadvancedglycationend-productsinthepancreaticbetacelllineHIT-T15.RegulPept.2012Aug20;177(1-3):79-84.

    [3].KubotaN,etal.Pioglitazoneamelioratesinsulinresistanceanddiabetesbybothadiponectin-dependentand-independentpathways.JBiolChem.2006Mar31;281(13):8748-55.

    [4].ElrashidyRA,etal.Pioglitazoneattenuatescardiacfibrosisandhypertrophyinaratmodelofdiabeticnephropathy.JCardiovascPharmacolTher.2012Sep;17(3):324-33.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.5452mL12.7259mL25.4518mL
5mM0.5090mL2.5452mL5.0904mL
10mM0.2545mL1.2726mL2.5452mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
CellAssay
[2]

Inordertoevaluatecellproliferation,HIT-T15cellsareseededon96-wellplates(3×104cells/well)andculturedfor5daysasdescribed.ViablecellsaredeterminedusingtheCellTiter96AqueousOneSolutionCellProliferationAssay.Toevaluatecellapoptosisandcellnecrosis,HIT-T15cellsareplatedon6-welldishes(7×105cells/well)for5daysinstandardconditions(CTR)orinthepresenceofAGEs(AGEs)withorwithoutPioglitazone(0.5or1μM)orAG(1mM).Theyarethenprocessedtomeasureboththeactivityofcaspase-3andtheactivityoflactatedehydrogenase(LDH)(astablecytosolicenzymethatisaMarkerofcellmembranedamageandcelldeathduetonecrosis)usingCytotox96NonRadioactiveCytotoxicityAssay[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[3][4]

Pioglitazone(AD4833)hydrochlorideispreparedin0.25%carboxymethylcellulose(Mice)[3].
PioglitazonehydrochlorideissUSPendedin0.5%carboxymethylcellulose(Rat)[4].

Mice[3]
10mg/kgPioglitazoneHClorvehicle(0.25%carboxymethylcellulose)isadnimisteredtoob/obandadipo-/-ob/obmicebyoralgavageoncedailyfor14consecutivedays.30mg/kgPioglitazoneorvehicleisalsoadnimisteredtoob/obandadipo-/-ob/obmicebyoralgavageoncedailyfor14consecutivedays.
Rat[4]
MaleWistaralbinorats(weighing250±20g)areued.Ratsthatachievedserumglucoselevel≥250mg/dLandserumcreatininelevel≥1.5mg/dLaredividedinto2groups(n=10pereachgroup):diabeticnephropathic(DN)groupinwhichratsreceivedanequalamountofvehicle(0.5%carboxymethylcellulose)andPioglitazone-treated(DN+Pio)groupinwhichratstreatedwithPioglitazone.Pioglitazone(10mg/kgBW)isgivenorallybygastricgavage,oncedaily,for4weeks.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References
  • [1].KuwabaraK,etal.Anovelselectiveperoxisomeproliferator-activatedreceptoralphaagonist,2-methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxane-r-2-carboxylicacid(NS-220),potentlydecreasesplasmatriglycerideandglucoseleve

    [2].PudduA,etal.Pioglitazoneattenuatesthedetrimentaleffectsofadvancedglycationend-productsinthepancreaticbetacelllineHIT-T15.RegulPept.2012Aug20;177(1-3):79-84.

    [3].KubotaN,etal.Pioglitazoneamelioratesinsulinresistanceanddiabetesbybothadiponectin-dependentand-independentpathways.JBiolChem.2006Mar31;281(13):8748-55.

    [4].ElrashidyRA,etal.Pioglitazoneattenuatescardiacfibrosisandhypertrophyinaratmodelofdiabeticnephropathy.JCardiovascPharmacolTher.2012Sep;17(3):324-33.

MolecularWeight

392.9

Formula

C₁₉H₂₁ClN₂O₃S

CASNo.

112529-15-4

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

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

10mMinDMSO

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

Purity:99.53%