XPO1-IN-1-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEXPO1-IN-1Cat.No.:HY-144763分⼦式:C₂₀H₁₅F₆N₅O₃S分⼦量:519.42作⽤靶点:Apoptosis;Others作⽤通路:Apoptosis;Others储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性XPO1-IN-1(compoundD4)⼀种⼝服有效的XPO1抑制剂,其在MM.1S细胞中的IC50为24nM。XPO1-IN-1能有效诱导细胞凋亡和细胞周期阻滞。XPO1-IN-1具有良好的代谢稳定性和药代动⼒学性质。XPO1-IN-1可⽤于多发性⾻髓瘤的研究[1]。IC50&TargetXPO1体外研究XPO1-IN-1(compoundD4)(24h)showshighanti-proliferationefficacyinMM.1Scellandlymphomatouscelllines[1].XPO1-IN-1(0-10μM,24h)inducescancercellcyclearrest[1].XPO1-IN-1(0-10μM,48h)inducesapoptosisofMM.1Scell[1].XPO1-IN-1(0-10μM,2h)inhibitsXPO1-dependentnuclearexport[1].XPO1-IN-1showsthegoodmetabolicstability,withmorethan80%intactcompoundremainedoverratplasma(2h),andaround85%intactcompoundremainedinlivermicrosomes(1h)[1].CellProliferationAssayCellLine:MM.1S,Mino,VAL,Rael,Namaiwa,Mutu,H9,JB6,andYT[1]Concentration:IncubationTime:24hResult:Showedhighanti-proliferationefficacyinMM.1Scellandlymphomatouscelllines(Mino,VAL,Rael,Namaiwa,Mutu,H9,JB6,andYT),withIC50valuesof24,80.2,189.1,201.8,77.7,158.2,101.1,154.1,and75.4nM,respectively.1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellCycleAnalysisCellLine:MM.1Scell[1]Concentration:0,0.1,1,5,and10μMIncubationTime:24hResult:Inducedcancercellcyclearrestinhighconcentration(>100nM),increasedthepopulationofcellsarrestedinG2to37.3%in5μM.ApoptosisAnalysisCellLine:MM.1Scell[1]Concentration:0,0.1,1,and10μMIncubationTime:48hResult:Inducedapoptosis,significantlyincreasedtheapoptoticcellrateto64.7%(10μM)whencomparedtothesamplewithnegativecontrol(6.7%).ImmunofluorescenceCellLine:MM.1Scell[1]Concentration:0,0.1,1,and10μMIncubationTime:2hResult:InhibitedXPO1-dependentnuclearexport.体内研究XPO1-IN-1(compoundD4)(SpragueDawleyrats;10mg/kg,IG;1mg/kg,IV;once)showsagoodpharmacokineticproperties[1].PharmacokineticParametersofXPO1-IN-1inSDrats[1].Parametersi.g.(10mg/kg)i.v.(1mg/kg)Tmax(h)2.17±1.760.08T1/2(h)2.12±0.162.32±0.17Cmax(ng/mL)1391.27±586.771239.08±152.54AUC0-t(ng/mL·h)5774.13±1461.411668.03±229.48AUC0-∞(ng/mL·h)6387.17±1637.181791.40±236.56CL(mL/h/kg)1638.65±431.97565.30±80.40F(%)34.6AnimalModel:SpragueDawleyrats[1]Dosage:10mg/kg(IG),1mg/kg(IV)Administration:Oralgavage(IG),IV,once(PharmacokineticAnalysis)Result:Showedagoodpharmacokineticproperties,withrelativelylonghalf-lifeof2.12h(IG)and2.32h(IV),respectively,anddecentbioavailabilityF(%)of34.6%.REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].QuB,etal.Design,synthesisandbiologicalevaluationofsulfonamidesinhibitorsofXPO1displayingactivityagainstmultiplemyelomacells.EurJMedChem.2022;235:114257.McePdfHeightCaution:Producthasnotbeenfullyvalidated