Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEDelanzomibCat.No.:HY-10454CASNo.:847499-27-8Synonyms:CEP-18770分?式:C??H??BN?O?分?量:413.28作?靶點:Proteasome;NF-κB;Apoptosis作?通路:MetabolicEnzyme/Protease;NF-κB;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(241.97mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.4197mL12.0983mL24.1967mL5mM0.4839mL2.4197mL4.8393mL10mM0.2420mL1.2098mL2.4197mL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%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.17mg/mL(5.25mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.17mg/mL(5.25mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.17mg/mL(5.25mM);ClearsolutionBIOLOGICALACTIVITY?物活性Delanzomib(CEP-18770)?種強(qiáng)效的具有?服活性的蛋?酶體的胰凝乳蛋?酶樣活性(chymotrypsin-likeactivityoftheproteasome)抑制劑，IC50為3.8nM。Delanzomib抑制NF-κB活性，誘導(dǎo)癌細(xì)胞凋亡(apoptotic)，并具有很強(qiáng)的抗?管?成和抗癌活性。IC50&TargetIC50:3.8nM(Chymotrypsin-likeactivityoftheproteasome)[1]體外研究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.體內(nèi)研究Delanzomib(CEP-18770;7.8-13mg/kg;oraladministration;twiceaweek;for4weeks)treatmentresultsinamoresustainedpharmacodynamicinhibitionofproteasomeactivityintumorsrelativetonormaltissues,completetumorregressionofmultiplemyeloma(MM)xenograftsandimprovesoverallmediansurvivalina2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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