CP-673451-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECP-673451Cat.No.:HY-12050CASNo.:343787-29-1分?式:C??H??N?O?分?量:417.5作?靶點:PDGFR作?通路:ProteinTyrosineKinase/RTK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(239.52mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3952mL11.9760mL23.9521mL5mM0.4790mL2.3952mL4.7904mL10mM0.2395mL1.1976mL2.3952mL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:≥2.75mg/mL(6.59mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.75mg/mL(6.59mM);ClearsolutionBIOLOGICALACTIVITY?物活性CP-673451?種有效的，選擇性的??板?長因?受體(PDGFR)抑制劑，抑制PDGFRα和PDGFRβ的活性，IC50值分別為10和1nM。IC50&TargetPDGFRαPDGFRβ10nM(IC50)1nM(IC50)體外研究CP-673451efficientlysuppressesthePDGFRdownstreamsignalingpathway.ItinhibitsphosphorylationofAkt,GSK-3β,p70S6,andS6inA549cellsinaconcentration-dependentmanner.CP-673451(0.0625-4μM)significantlyreducestheviabilityofNSCLCcelllinesA549andH1299inatime-andconcentration-dependentmanner,withIC50sof0.49and0.61μM,respectively.CP-673451(1,4μM)inducesapoptosisinnon-small-celllungcancercells.CP-673451(25,100,or400nM)iseffectiveatinhibitingmigrationandinvasionofNSCLCcellsbysuppressionoflamellipodiaformation[1].CP-673451andcrenolanibshowselectivelethalitytowardcellswithCA.U2OScellstreatedwith1to4μMCP-673451orcrenolanibshowaruffledcellsurfaceasasignforalterationsofthecorticalactincytoskeleton.CP-673451attenuatesPDGF-BB-inducedsignaling,andsignificantlyenhancesthephosphorylationofPDGFR-βdownstreameffectors,AktandMEK[2].CP-673,451(0.5μM)regulatescellproliferationthroughmechanismsinvolvingreducedphosphorylationofGSK-3αandGSK-3β.CP-673,451impairsrhabdosphere-formingcapacityinbothRDandRUCH2cultures[3].CP-673,451inhibitsPDGFR-βinPAE-βcellswithanIC50valueof6.4nM.Besides,CP-673,451incubationinH526andPAE-βcellsresultsinanIC50valueof1.1μMagainstc-kit[4].體內(nèi)研究CP-673451(20mg/kg)leadstoamediumsuppressionoftumorgrowth,whilehigh-doseCP-673451(40mg/kg)stronglyinhibitstumorgrowthinmicewithoutsignificantweithtloss[1].CP-673,451(10,33,and100mg/kg,p.o.,b.i.d)inhibitsthegrowthofColo205tumorinadose-dependentmanner,andsimilartumorgrowthinhibitionexperimentscompletesonLS174T,H460,andU87MGxenografts,withnosignsofmorbidityorweightloss[4].PROTOCOLCellAssay[3]Cellproliferation/viabilityisanalyzedusingtheCyQuantproliferationassay.Pre-starvedcellsaretreatedevery24hourswithvehicle(dimethylsulfoxide)or0.5μMCP-673,451dilutedinserum-reducedmedium(1.5%FBS)for96hours.Theamountofnucleicacidpresentinlysedcellsisnormalizedtotheamountwhentreatmentisinitiated.Cellproliferation/viabilityinresponseto300ng/mLPDGF-CCislikewiseanalyzed,butcellsarethenkeptinserum-freemediumandtreatedtwiceduringa48-hourperiod.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAsubcutaneousA549xenograftmodelinnudemiceisusedtoevaluatetheanticanceractivityofCP-2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration[1]673451.Briefly,A549cellsareinjectedintotheaxillaryregionsofmice(2×106cells/mouse).Whenthetumorvolumesreach70mm3,themicearerandomlyassignedtoacontrolgroupandtwoCP-673451groups(n=6pergroup):low-dose(20mg/kg)andhighdose(40mg/kg)groups(vehicle10%1-methyl-2-pyrrolidinoneand90%polyethyleneglycol300).TheseanimalsareadministeredintraperitoneallywithCP-673451(20or40mg/kg/day)orwithvehicle.Duringthetreatmentperiod,theimplantedtumorsaremeasuredbycaliperonceadayinablindfashion.Theanimalbodyweightsarealsomeasuredatthesametime.Thetumorvolumeiscalculated.Aftertreatment,themicearekilled,andthetumorsareharvestedandanalyzed.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ClinCancerRes.2019Feb1;25(3):1070-1086.?Glia.2020Feb;68(2):345-355.?JInvestDermatol.2019Jul;139(7):1574-1582.?FASEBJ.2016Nov;30(11):3733-3744.?AmJTranslRes.2020Jul15;12(7):3577-3595.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].XiY,etal.CP-673451,aplatelet-derivedgrowth-factorreceptorinhibitor,suppresseslungcancercellproliferationandmigration.OncoTargetsTher.2014Jul3;7:1215-21.[2].KonotopG,etal.PharmacologicalInhibitionofCentrosomeClusteringbySlingshot-MediatedCofilinActivationandActinCortexDestabilization.CancerRes.2016Nov15;76(22):6690-6700[3].EhnmanM,etal.Distincteffectsofligand-inducedPDGFRαandPDGFRβsignalinginthehumanrhabdomyosarcomatumorcellandstromacellcompartments.CancerRes,2013,73(7),2139-2149.[4].RobertsWG,etal.AntiangiogenicandantitumoractivityofaselectivePDGF