Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECADD522Cat.No.:HY-107999CASNo.:199735-88-1分?式:C??H??Cl?NO?分?量:326.17作?靶點(diǎn):ReactiveOxygenSpecies作?通路:Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κB儲(chǔ)存?式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:250mg/mL(766.47mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.0659mL15.3294mL30.6589mL5mM0.6132mL3.0659mL6.1318mL10mM0.3066mL1.5329mL3.0659mL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(storedundernitrogen)。-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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)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:≥2.17mg/mL(6.65mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.17mg/mL(6.65mM);Clearsolution1/5MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性CADD522?種RUNX2-DNA結(jié)合抑制劑(下調(diào)RUNX2介導(dǎo)的下游靶因的轉(zhuǎn)錄)，其IC50值為10nM。CADD522還可通過(guò)增加線粒體驅(qū)動(dòng)的細(xì)胞ROS?平發(fā)揮其抗腫瘤活性。CADD522能抑制體內(nèi)原發(fā)腫瘤的?長(zhǎng)和免疫受損??肺部腫瘤細(xì)胞的實(shí)驗(yàn)性轉(zhuǎn)移，可?于癌癥的研究。IC50&TargetRUNX2-DNAbinding[1]體外研究CADD522(0-100μM;24-72h)exhibitsastronginhibitoryeffectonBCcellgrowthandsurvival[1].CADD522(50μM;72h)showsanti-proliferativeeffectbyinducingcellcyclearrest(G1phase)[1].CADD522(50μM;8days)inhibitstumorsphereformationand(50μM;24h)invitroinvasionofBCcells(withoutcellulartoxicity)[1].CADD522(2,10,25,50,100μM;48h)inhibitsRUNX2transcriptionalactivitybyinhibitingRUNX2-DNAbindinginT47D-RUNX2andT47D-Emptycells[1].CADD522(50μM;72h)upregulatesRUNX2levelsthroughincreasedRUNX2stabilityincells[1].CADD522(50μM;6or24h)increasesROSgenerationofmitochondrialinMCF7andMDA-468cells[2].CADD522(0-2000nM,30min)inhibitsmitochondrialATPsynthaseactivityinMDA-231andMDA-468cells[2].CellViabilityAssay[1]CellLine:MDA-MB-468,MCF7,MCF10A,IEC-6,GES-1andC2C12cellsConcentration:0-100μMIncubationTime:24-72hResult:Displayedadose-andtime-dependentcellgrowthinhibitionover72h.Exhibitedlowcytotoxicityfornormalcellgrowth.CellCycleAnalysis[1]CellLine:MCF7,MDA-468andMDA-231cellsConcentration:50μMIncubationTime:72hResult:InducedMDA-231cellsaccumulatedattheG1andG2/MphasewhereasMCF7andMDA-468cellswereattheG1phase.CellViabilityAssay[1]CellLine:MCF7,MCF7-tet-offcellsConcentration:50μM2/5MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:8daysResult:Dramaticallydecreasedthesizeaswellasthenumberoftumorspheres,andseverelydisruptedtumorspheresatday4.ShowedarelativelyselectiveeffectonBCcells(didnothaveasignificantinfluenceonmammosphereformationoftheMCF10Anon-malignantmammaryepithelialcells).CellInvasionAssay[1]CellLine:MCF7-tet-off(+Doxy),MCF7-tet-off(-Doxy)cellsConcentration:50μMIncubationTime:24hResult:AlmostabrogatedtheinvasivenessofbothMCF7-tet-off(+Doxy)andMCF7-tet-off(-Doxy)cellswithoutcellulartoxicity.CellViabilityAssay[1]CellLine:T47D-RUNX2andT47D-EmptycellsConcentration:2,10,25,50,100μMIncubationTime:48hResult:Resultedinadramaticdecreaseofthepromoter-luciferase(Luc)activitiesofRUNX2downstreamtargetgenessuchasMMP13andVEGF(metastasismarkers)andOC(osteogenesismarker).RT-PCR[1]CellLine:T47DandMCF7cells(ectopicexpressingRUNX2)Concentration:50μMIncubationTime:72hResult:SignificantlyinhibitedthemRNAlevel(RUNX2-mediated)ofGlut-1andLDHA.WesternBlotAnalysis[1]CellLine:T47D-RUNX2andMCF7-RUNX2cellsConcentration:50μMIncubationTime:72hResult:EnhancedbothmRNAandproteinexpressionofRUNX2.3/5MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEWesternBlotAnalysis[1]CellLine:MDA-468andMDA-231cellsConcentration:50μMIncubationTime:2,4,6hResult:IncreasedRUNX2stabilitybydelayingproteindegradation.CellViabilityAssay[2]CellLine:MCF7andMDA-468cellsConcentration:50μMIncubationTime:6or24hResult:IncreasedthelevelofmitochondrialROS,whichwasmoreevidentinserum-freethanserum-containingcondition.CellViabilityAssay[2]CellLine:MDA-231andMDA-468cellsConcentration:50,250,2000nM(forMDA-231);500,2000nM(forMDA-468)IncubationTime:30minResult:InhibitedtheactivityofATPsynthase.體內(nèi)研究CADD522(1,5and20mg/kg;i.p.;twiceaweekfor45days)delaystheonsetofthetumorsandsuppressestumorgrowthinmice[1].CADD522(10mg/kg;i.p.;twiceaweekfor11days)suppressestumormetastasisandinhibitsexpressionofKi-67inmice[1].AnimalModel:Femalemice(6-week-old;MMTV-PyMTtransgenicmodel)[1].Dosage:1,5and20mg/kgAdministration:Intraperitonealinjection;twiceaweekfor45days.Result:Delayedtheonsetofthetumors,delayedtumordevelopmentandreducedtumorburdenintransgenicMMTV-PyMTmice.Reducedthetumorweightinmice.AnimalModel:FemaleNODscidgamma(NSG)miceandnudemice(TNBC-PDXBr-001model)[1].4/5MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDosage:10mg/kgAdministration:Intraperitonealinjection;twiceaweekfor11days.Result:SignificantdecreasedtumorvolumeandmarkedlyinhibitedexpressionofKi-67.InhibitedexperimentalmetastasisofBCcellsinvivo.(didnotsignificantlydecreasebodyweightorinfluencethegeneralhealthofanimals).戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatCommun.