VIT-2763-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVIT-2763Cat.No.:HY-112220CASNo.:2095668-10-1分?式:C??H??FN?O?分?量:408.43作?靶點:Ferroportin作?通路:MembraneTransporter/IonChannel儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:125mg/mL(306.05mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.4484mL12.2420mL24.4840mL5mM0.4897mL2.4484mL4.8968mL10mM0.2448mL1.2242mL2.4484mL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(fù)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(dāng)?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(dāng)保存；體內(nèi)實驗的?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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(5.09mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.09mM);ClearsolutionBIOLOGICALACTIVITY?物活性VIT-2763具有?服活性的鐵轉(zhuǎn)運蛋?(ferroportin)的抑制劑，抑制hepcidin與鐵轉(zhuǎn)運蛋?結(jié)合，阻滯鐵外流。VIT-2763有?于地中海貧?癥的潛?。體外研究VIT-2763dosedependentlyreducesthefluorescencepolarizationsignal,indicatingthatVIT-2763displacesTMR-hepcidinfromferroportin(IC50of24±13nM)[1].VIT-2763inducesBLAreportergeneactivitywithanaverageEC50of140±50nM,asaconsequenceofincreasingintracellularironconcentrationscausedbyblockedironexportinHEK293cells[1].VIT-2763(100nM)triggersubiquitinationandsubsequentinternalizationanddegradationofferroportin[1].CellViabilityAssay[1].CellLine:J774cells.Concentration:100nM.IncubationTime:10,20,40,60,or120minutes.Result:Inducedferroportininternalizationandubiquitination.體內(nèi)研究VIT-2763(30,100mg/kg,orallytwicedailyfor36days)decreasesserumironandpreventedliverironloadinginHbbth3/+mice[1].VIT-2763didnotchangethetotalliveriron[1].VIT-2763(30,100mg/kg,orallytwicedailyfor36days)significantlycorrectsanemiaandimprovedRBCparametersinHbbth3/+mice.VIT-2763decreasesthepercentageofROS-positiveRBCsinHbbth3/+micefrom67%to30%[1].VIT-2763decreasesapoptosisandextendsthelifespanofRBCsinHbbth3/+mice[1].AnimalModel:Hbbth3/+mice[1].Dosage:30,100mg/kg.Administration:Orallytwicedailyfor36days.Result:Significantlydecreasedserumironlevelsby77%(30mg/kg)and84%(100mg/kg),SignificantlyincreasedHblevels(asofday8oftreatment),RBCcounts,meancorpuscularHbconcentration(MCHC),andsignificantlyloweredreticulocytecounts,meancorpuscularHb(MCH),meancorpuscularvolume(MCV),andRBCdistributionwidth(RDW)inHbbth3/+mice,ascomparedwiththeHbbth3/+vehiclegroup.REFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].VaniaManolova,etal.OralFerroportinInhibitorAmelioratesIneffectiveErythropoiesisinaModelofβ-Thalassemia.JClinInvest.2019Dec9;130(1):491-506.McePdfHeightCaution:Producthasnotbeenfullyvalidated