Delanzomib-CEP-18770-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEDelanzomibCat.No.:HY-10454CASNo.:847499-27-8Synonyms:CEP-18770分⼦式:C₂₁H₂₈BN₃O₅分⼦量:413.28作⽤靶点:Proteasome;NF-κB;Apoptosis作⽤通路:MetabolicEnzyme/Protease;NF-κB;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(241.97mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4197mL12.0983mL24.1967mL5mM0.4839mL2.4197mL4.8393mL10mM0.2420mL1.2098mL2.4197mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.17mg/mL(5.25mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.17mg/mL(5.25mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.17mg/mL(5.25mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Delanzomib(CEP-18770)⼀种强效的具有⼝服活性的蛋⽩酶体的胰凝乳蛋⽩酶样活性(chymotrypsin-likeactivityoftheproteasome)抑制剂，IC50为3.8nM。Delanzomib抑制NF-κB活性，诱导癌细胞凋亡(apoptotic)，并具有很强的抗⾎管⽣成和抗癌活性。IC50&TargetIC50:3.8nM(Chymotrypsin-likeactivityoftheproteasome)[1]体外研究Delanzomib(CEP-18770;20nM;12-24hours)treatmentresultsinaprogressiveappearanceofcleavedcaspases-3,-7,and-9between12and24hours’exposureinthehumanMMcelllines,RPMI-8226,andU266[1].Delanzomib(CEP-18770;5-40nM;4-24hours)treatmentinducesanaccumulationofubiquitinatedproteinsover4to8hours[1].Delanzomib(CEP-18770)inhibitsendothelialcellsurvival,vasculogenesis,andosteoclastogenesisinvitro;anddisplaysafavorablecytotoxicityprofiletowardnormalcells[1].ApoptosisAnalysis[1]CellLine:RPMI-8226,U266,andK562cellsConcentration:20nMIncubationTime:12hours,24hoursResult:Resultedinaprogressiveappearanceofcleavedcaspases-3,-7,and-9between12and24hours’exposureinthehumanMMcelllines.WesternBlotAnalysis[1]CellLine:RPMI-8226,U266,andK562cellsConcentration:5nM,10nM,20nM,40nMIncubationTime:4hours,8hours,12hours,24hoursResult:Inducedanaccumulationofubiquitinatedproteinsover4to8hours.体内研究Delanzomib(CEP-18770;7.8-13mg/kg;oraladministration;twiceaweek;for4weeks)treatmentresultsinamoresustainedpharmacodynamicinhibitionofproteasomeactivityintumorsrelativetonormaltissues,completetumorregressionofmultiplemyeloma(MM)xenograftsandimprovesoverallmediansurvivalina2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEsystemicmodelofhumanMM[1].AnimalModel:SCIDmiceinjectedwithRPMI8226cells[1]Dosage:7.8mg/kg,10mg/kg,13mg/kgAdministration:Oraladministration;twiceaweek;for4weeksResult:Resultedinamoresustainedpharmacodynamicinhibitionofproteasomeactivityintumorsrelativetonormaltissues.REFERENCES[1].PivaR,etal.CEP-18770:Anovel,orallyactiveproteasomeinhibitorwithatumor-selectivepharmacologicprofilecompetitivewithbortezomib.Blood.2008Mar1;111(5):2765-75.McePdfHeightCaution:Producthasnotbee