Anagliptin-hydrochloride-SK-0403-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAnagliptinhydrochlorideCat.No.:HY-14877ACASNo.:1359670-56-6Synonyms:SK-0403hydrochloride分?式:C??H??ClN?O?分?量:419.91作?靶點:DipeptidylPeptidase作?通路:MetabolicEnzyme/Protease儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Anagliptin(SK-0403)hydrochloride?種?選擇性的、有效的、具有?服活性的?肽酰肽酶4(DPP-4)抑制劑，IC50值為3.8nM，對DPP-8和DDP-9的選擇性相對較弱，IC50值分別為68nM和60nM。IC50&TargetDPP-IVDPP-9DPP-83.8nM(IC50)60nM(IC50)68nM(IC50)體外研究Anagliptin(SK-0403)(0-100μM;24h)attenuatess-DPP-4-inducedsmoothmusclecellsproliferation[2].Anagliptin(100μM;10min)reducesTNF-αproductioninculturedmonocytes[2].Anagliptin(0.001-10μM;24h)significantlysuppressessterolregulatoryelement‐bindingproteinactivityinHepG2cells(21%decrease)[3].CellProliferationAssay[2]CellLine:Ratsmoothmusclecells(SMC)Concentration:1,10and100μMIncubationTime:24hResult:Attenuateds-DPP-4-inducedSMCproliferationinadose-dependentmanner.InhibitedLPS-inducedERKphosphorylationandmarkedlysuppressedLPS-inducednucleartranslocationofNF-κBp65.WesternBlotAnalysis[2]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:Ratsmoothmusclecells(SMC)Concentration:100μMIncubationTime:10minResult:Blockedtheearly-butnotthelate-phaseERKphosphorylationinducedbys-DPP-4.體內(nèi)研究Anagliptin(SK-0403)(0.3%;indiet;16weeks)reducesatheroscleroticlesionanddoesnotincreasethenumberofcirculatingEPCsinapoliporoteinE(apoE)-deficientmice[2].Anagliptin(0.3%;indiet;4weeks)exhibitsalipid‐loweringeffectinahyperlipidemicmicemodel[3].AnimalModel:MaleapoliporoteinE(apoE)-deficientmice[2]Dosage:0.3%Administration:Indiet,16weeksResult:ReducedDPP-4activityintheplasmaasexpectedanddidnotaffectfoodconsumptionorbodyweightgain.Significantlyreducedtotalcholesterollevel,especiallyVLDLandLDL-Cwithoutaffectingtriglyceridelevel.Alsodecreasedtheα-SMA-positiveareawithintheindividualplaque.AnimalModel:Malelow‐densitylipoproteinreceptor‐deficientmice(B6.129S7‐Ldlrtm1Her/J)[3]Dosage:0.3%Administration:Indiet,4weeksResult:Significantlydecreasedtheplasmatotalcholesterol(14%reduction)andtriglyceridelevels(27%reduction).Significantlydecreasedlow‐densitylipoproteincholesterolandvery

low‐densitylipoproteincholesterol.Sterolregulatoryelement‐bindingprotein‐2messenger

ribonucleicacidexpressionlevelwassignificantlydecreasedatnight.AnimalModel:MaleSprague–DawleyratsandBeagledogs[1]Dosage:0.2,0.5,1and10mg/kgAdministration:Oralorintravenousadministration(PharmacokineticStudies)Result:SelectedPKparametersofAnagliptinhydrochlorideinratsanddogs[1]CompoundSpeciesCLtot(l/h/kg)Vdss(l/h/kg)Cmaxc(ng/ml)Tmaxc2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE(h)T1/2(h)AUC(ng/h/ml)BA(%)AnagliptinhydrochlorideaRat2.00(iv)0.68(iv)309(62)(po)0.8(2.3)(po)1.9(po)1160(po)23(po)Dog0.65(iv)0.83(iv)261(po)1.5(po)1.0(po)824(po)100(po)aAnagliptinhydrochloridedoseinrats,1mg/kg,iv(n=3);10mg/kg,po(n=3).4adoseindogs,0.2mg/kg,iv(n=3);0.5mg/kg,po(n=2).cValuesinparentheseswereobtainedatadoseof3mg/kg(n=3).戶使?本產(chǎn)品發(fā)表的科研?獻?BiochemPharmacol.2018Oct;156:312-321.?MolMedRep.2017Dec;16(6):8003-8010.?ExpTherMed.February15,2022.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].KatoN,etal.DiscoveryandpharmacologicalcharacterizationofN-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamidehydrochloride(anagliptinhydrochloridesalt)asapotentandselectiveDPP-IVinhibitor.BioorgMedChem.2011Dec1;19(23):7221-7.[2].ErvinnaN,etal.Anagliptin,aDPP-4inhibitor,suppressesproliferationofvascularsmoothmusclesandmonocyteinflammatoryreactionandattenuatesatherosclerosisinmaleapoE-deficientmice.Endocrinology.2013Mar;154(3):1260-70.[3].YanoW,etal.Mechanismoflipid-loweringactionofthedipeptidylpeptidase-4inhibitor,anagliptin,inlow-densitylipoproteinreceptor-deficientmice.JDiabetesInvestig.2017Mar;8(2):