Canagliflozin-JNJ-28431754-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECanagliflozinCat.No.:HY-10451CASNo.:842133-18-0Synonyms:JNJ28431754分?式:C??H??FO?S分?量:444.52作?靶點(diǎn):SGLT作?通路:MembraneTransporter/IonChannel儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥50mg/mL(112.48mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.2496mL11.2481mL22.4962mL5mM0.4499mL2.2496mL4.4992mL10mM0.2250mL1.1248mL2.2496mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：1%DMSO>>99%salineSolubility:≥0.5mg/mL(1.12mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.62mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.62mM);Clearsolution4.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.62mM);Clearsolution5.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(5.62mM);Clearsolution6.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.62mM);ClearsolutionBIOLOGICALACTIVITY?物活性Canagliflozin(JNJ28431754)?種選擇性的SGLT2抑制劑，作?于表達(dá)mSGLT2，rSGLT2和hSGLT2的CHO細(xì)胞，IC50分別為2nM，3.7nM和4.4nM[1]。IC50&TargetIC50:2/3.7/4.4nM(mSGLT2/rSGLT2/hSGLT2,inCHOKcells)[1]體外研究CanagliflozininhibitsNa+-dependent14C-AMGuptakeinCHO-hSGLT2cells,withanIC50of4.4±1.2nM.SimilarIC50valuesareobtainedinCHO-rSGLT2andCHO-mSGLT2cells(IC50=3.7and2.0nMforratandmouseSGLT2,respectively).Canagliflozininhibits14C-AMGuptakeinCHO-hSGLT1andmSGLT1cellswithIC50of684±159nMand>1,000nM,respectively[1].體內(nèi)研究Canagliflozin(30mg/kgtreatmentfor4weeks)reducesbloodglucose(BG)levels,respiratoryexchangeratio,andbodyweightgaininDIOmice[1].Canagliflozin(3mg/kgfor3weeks)increasesurinaryglucoseexcretion(UGE)withnosignificantchangeintotalfoodintakecomparedwiththatinvehicle-treatedrats,leadingtoadecreaseinbodyweightInZFrats[1].AnimalModel:Diet-inducedobese,insulinresistantmice(DIO)Mice[1]Dosage:30mg/kgAdministration:Oralgavage;daily;4weeksResult:ReducedBGlevels,respiratoryexchangeratio,andbodyweightgain.AnimalModel:MaleZuckerfatty(ZF)obese,insulinresistantrats[1]Dosage:3mg/kgAdministration:Oralgavage;daily;3weeks2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:UGEwasincreasedwithnosignificantchangeintotalfoodintakecomparedwiththatinvehicle-treatedrats,leadingtoadecreaseinbodyweight.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Nature.2018Aug;560(7719):499-503.?NatCellBiol.2022May30.?MolCell.2020Oct1;80(1):87-101.e5.?CardiovascRes.02November2020.?MolMetab.2019Jan;19:1-12.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LiangY,etal.Effectofcanagliflozinonrenalthresholdforglucose,glycemia,andbodyweightinnormalanddiabeticanimalmodels.PLoSOne.2012;7(2):e30555.McePdfHeightCaution:Producthasnotbe