FD223-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEFD223Cat.No.:HY-132231CASNo.:2050524-24-6分?式:C??H??ClN?O?S分?量:385.83作?靶點(diǎn):PI3K;Apoptosis作?通路:PI3K/Akt/mTOR;Apoptosis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:100mg/mL(259.18mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.5918mL12.9591mL25.9182mL5mM0.5184mL2.5918mL5.1836mL10mM0.2592mL1.2959mL2.5918mL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.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.48mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(6.48mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性FD223?種有效且選擇性的磷酸肌醇3-激酶δ(PI3Kδ)抑制劑。FD223顯?出?效價(jià)(IC50=1nM)和對(duì)其他異構(gòu)體的良好選擇性(α、β和γ的IC50值分別為51nM、29nM和37nM）。FD223通過抑制p-AKTSer473有效抑制急性髓系??病(AML)細(xì)胞系的增殖，從?導(dǎo)致細(xì)胞周期G1期阻滯。FD223在AML等??病的研究中具有潛?。IC50&TargetPI3KδPI3KαPI3KβPI3Kγ1nM(IC50)51nM(IC50)29nM(IC50)37nM(IC50)體外研究FD223exhibitsnotableanti-proliferativeactivitiesinthep110δ-positiveAMLcelllinesHL-60,MOLM-16,EOL-1andKG-1,withtheIC50of2.25μM,0.87μM,2.82μM,and5.82μM,respectively.FD223showsweakanti-proliferativeactivityagainstp110δunexpressedMM.1Rcellline,withtheIC50valueof23.13μM[1].FD223(MOLM-16cells;0.1-5μM;16hours)dose-dependentlyreducesphosphorylationofAkt(Ser473),whichisconsistentwiththepositivecontrolIdelalisib,illustratingthattheactivityofPI3K/AktpathwayinMOLM-16cellisblocked[1].FD223(MOLM-16cells;24hours;1-5μM)arreststhecellcycleattheG1phasesimilartothatofpositivecontrolIdelalisib[1].FD223(1-5μM;48hours)dose-dependentlyinducescellularapoptosis[1].ApoptosisAnalysis[1]CellLine:MOLM-16cellsConcentration:1-5μMIncubationTime:48hoursResult:Dose-dependentlyinducedcellularapoptosis,whichissuperiortothatofpositivecontrolIdelalisib.WesternBlotAnalysis[1]CellLine:MOLM-16cellsConcentration:0.1-5μMIncubationTime:16hoursResult:Dose-dependentlyreducedphosphorylationofAkt(Ser473).體內(nèi)研究FD223(20and40mg/kg;p.o,perdayfor14consecutivedays)displayspotentantitumorefficacyinMOLM-2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE16xenograftmodelwiththetumorvolumereductionof49%atadoseof40mg/kg/day(po),andshowsnosignificanttoxicityinthepreliminarysafetyassessment[1].FD223(i.v.;doseof2mg/kg;p.o.;10mg/kgrats)showsamoderateplasmaclearancerateafterintravenousadministrationwithC=0.191L?h-1?kg-1.Intheporoute,itshowsahalf-life(t1/2)of3.74handaCmaxof1104ng/mL,goodoralplasmaexposures(AUC0-∞>9000h?ng/mL)andacceptableoralbioavailability(17.6%)[1].AnimalModel:MOLM-16xenograftmodelofBALB/cnudemice[1]Dosage:20and40mg/kgAdministration:P.o,perdayfor14consecutivedaysResult:Showedadose-dependenttumorgrowthinhibition(TGI)of31%for20mg/kgand49%for40mg/kgREFERENCES[1].YangC,etal.BioisostericreplacementsoftheindolemoietyforthedevelopmentofapotentandselectivePI3Kδinhibitor:Design,synthesisandbiologicalevaluation[publishedonlineaheadofprint,2021Jun21].EurJMedChem.2021;223:113661.McePdfHeightCaution:Produ