Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESeladelparCat.No.:HY-19522CASNo.:851528-79-5Synonyms:MBX-8025分?式:C??H??F?O?S分?量:444.46作?靶點:PPAR作?通路:CellCycle/DNADamage儲存?式:Pureform-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(224.99mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2499mL11.2496mL22.4992mL5mM0.4500mL2.2499mL4.4998mL10mM0.2250mL1.1250mL2.2499mL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；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。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：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(5.62mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.62mM);ClearsolutionBIOLOGICALACTIVITY?物活性Seladelpar(MBX-8025)?種有效的，具有?服活性的，特異性PPAR-δ激動劑，EC50為2nM[1][2]。IC50&TargetPPAR-δPPAR-α2nM(EC50)1600nM(EC50)體外研究Seladelpar(MBX-8025)isanorallyactive,potent(2nM),andspecific(>750-foldand>2500-foldcomparedwithPPAR-αorPPAR-γreceptors,respectively)PPAR-δagonistbeingdevelopedasalipid-alteringagent[1].Seladelparisapotent,andselectivePPAR-δagonist(50%effectconcentrationhumanPPAR-δ=2nM,PPAR-α=1,600nM)thatdemonstratesfavorableeffectsoninsulinresistance,diabetes,andatherogenicdyslipidemia[2].體內(nèi)研究Fromweaning,femaleAlms1mutant(foz/foz)miceandwild-typelittermatesarefedanatherogenicdietfor16weeks;groups(n=8-12)arethenrandomizedtoreceiveSeladelpar(10mg/kg)orvehicle(1%methylcellulose)bygavagefor8weeks.Despiteminimallyalteringbodyweight,Seladelparnormalizeshyperglycemia,hyperinsulinemia,andglucosedisposalinfoz/fozmice.Serumalanineaminotransferaseranges300-600U/Linvehicle-treatedfoz/fozmice;Seladelparreducesalanineaminotransferaseby50%.Inaddition,Seladelparnormalizesserumlipidsandhepaticlevelsoffreecholesterolandotherlipotoxiclipidsthatareincreasedinvehicle-treatedfoz/fozversuswild-typemice.Thisabolishedhepatocyteballooningandapoptosis,substantiallyreducesteatosisandliverinflammation,andimproveliverfibrosis.Invehicle-treatedfoz/fozmice,themeannonalcoholicfattyliverdiseaseactivityscoreis6.9,indicatingnonalcoholicsteatohepatitis(NASH);SeladelparreversesNASHinallfoz/fozmice(nonalcoholicfattyliverdiseaseactivityscore3.13).Inatherogenicdiet-fedWtmice,administrationofSeladelparreducesbodyweightby-18%(Pfoz/fozmice.Theseanimalsdevelopeseverehyperglycemia,hyperinsulinemia,andwhole-bodyinsulinresistanceafter16weeks(Pfoz/fozmice(Pfoz/fozmice(PWtmice(P[2].PROTOCOLAnimalMice[2]Administration[2]Fromweaning(week4),Alms1mutant(foz/foz)NOD.B10miceorWtlittermates(femalemiceinbothgroups)arefedanatherogenicdiet(23%fat,0.2%cholesteroland45%simplecarbohydrate;4.78kcal/gdigestibleenergy)adlibitumfor16weeks,afterwhichgroupsarerandomized(n=8-12mice/group)toonce-a-dayoraladministration(bygavage)for8weeksofSeladelpar(10mg/kgin1%methylcellulose)orvehicle(controls).Animalsarehousedunder12-hourlight/darkcycleandconstanttemperatureof22°Candreceivemaximalhumanecare[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].BaysHE,etal.MBX-8025,anovelperoxisomeproliferatorreceptor-deltaagonist:lipidandothermetaboliceffectsindyslipidemicoverweightpatientstreatedwithandwithoutatorvastatin.JClinEndocrinolMetab.2011Sep;96(9):2889-97.[2].HaczeyniF,etal.Theselectiveperoxisomeproliferator-activatedreceptor-deltaagonistseladelparreversesnonalcoholicsteatohepatitispathologybyabrogatinglipotoxicityindiabeticobesemice.HepatolCommun.2017Jul31;1(7):663-674