ODM-203-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEODM-203Cat.No.:HY-119367CASNo.:1430723-35-5分?式:C??H??F?N?O?S分?量:505.54作?靶點(diǎn):FGFR;VEGFR作?通路:ProteinTyrosineKinase/RTK儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:66.67mg/mL(131.88mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.9781mL9.8904mL19.7808mL5mM0.3956mL1.9781mL3.9562mL10mM0.1978mL0.9890mL1.9781mL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。-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(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(4.11mM);Clearsolution1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.11mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.11mM);ClearsolutionBIOLOGICALACTIVITY?物活性O(shè)DM-203?種?服有效的，具有選擇性的FGFR/VEGFR抑制劑，其對(duì)FGFR3/1/2和VEGFR3/2/1/4的IC50值分別為6,11,16,5,9,26和35nM。ODM-203具有很強(qiáng)的抗腫瘤活性，并能激活腫瘤微環(huán)境中的免疫反應(yīng)。IC50&TargetFGFR1FGFR2FGFR3FGFR411nM(IC50)16nM(IC50)6nM(IC50)35nM(IC50)VEGFR1VEGFR2VEGFR3DDR126nM(IC50)9nM(IC50)5nM(IC50)6nM(IC50)RETSIK3PDGFRaMINK18nM(IC50)23nM(IC50)35nM(IC50)41nM(IC50)MAP4K449nM(IC50)體外研究ODM-203(eight-doseconcentrationseriesupto3μM;96h)potentlyinhibitsFGFRsignalingandproliferationinseveralFGFR-dependentcelllines[1].ODM-203(eight-doseconcentrationseriesupto3μM;10days)inhibitsendothelialtubuleformation[1].ODM-203(1,10,100,1000nM;1h)inhibitingFGFRandVEGFRcellularsignalinginHUVECcells[1].CellViabilityAssay[1]CellLine:H1581(ATCC-CRL-5878),SNU16(ATCC-CRL-5974)andRT4(HTB2)cellsConcentration:Eight-doseconcentrationseriesupto3μMIncubationTime:96hResult:Suppressedcellproliferationinadose-dependentmannerinH1581(IC50=104nM),SNU16(IC50=132nM)andRT4cells(IC50=192nM).CellViabilityAssay[1]CellLine:HUVECsandhumanumbilicalveinendothelialcells(co-culture)Concentration:Eight-doseconcentrationseriesupto3μMIncubationTime:10days(mediaandtestagentswerereplacedevery2-3days)2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:Inhibitedendothelialtubuleformationinadose-dependentmanneratnon-toxicconcentrationswithanIC50valueof33nM.WesternBlotAnalysis[1]CellLine:HUVECcellsConcentration:1,10,100,1000nMIncubationTime:1hResult:SuppressedbothFGFRandVEGFRsignaling.體內(nèi)研究ODM-203(20,40mg/kg;p.o.;singledailyfor21days)inhibitsFGFRphosphorylationandtumorgrowthinseveralFGFR-dependentxenograftsbysuppressingFGFRsignalingintumors[1].ODM-203(7,20,40mg/kg;p.o.;singledailyfor21days)showsstronganti-tumoractivityinaVEGFR-dependentangiogenicorthotopicsyngenicmodel(Renca)andsuppressesangiogenesis[1].ODM-203(20,40mg/kg;p.o.;singledailyfor5days)activatesimmuneresponseinthetumormicroenvironment[1].AnimalModel:AthymicNude-Foxn1nufemalemice(9-week-old;subcutaneousxenograftmodels)[1].Dosage:20,40mg/kgAdministration:Oraladministration;singledailyfor21days.Result:Significantlyinhibitedtumourgrowthfor21consecutivedays.Showedtumorgrowthinhibition(TGI)inRT4xenograftswas37%and92%withdosageof20and40mg/kg,respectively.AnimalModel:Malebalb/cmice(8-week-old;orthotopicrencasyngenicmodel)[1].Dosage:7,20,40mg/kgAdministration:Oraladministration;singledailyfor21days.Result:Showedtumorgrowthinhibitionwere39%,58%and75%fordosageof7,20and40mg/kg,respectively.Inhibitedformationoflungmetastasis,andsuppressedangiogenesis.AnimalModel:Malebalb/cmalemice(5to7-week-old;rencasubcutaneoustumormodel)[1].Dosage:20,40mg/kgAdministration:Oraladministration;singledailyfor5days.3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:ResultedinanincreaseinthepercentageoftotalandCD4Tcells.DecreasedtheexpressionofimmunecheckpointsPD-1andPD-L1andincreasedIFN-γexpressiononbothCD8TcellsandNKcells.REFERENCES[1].Holmstr?mTH,etal.ODM-203,aSelectiveInhibitorofFGFRandVEGFR,ShowsStrongAntitumorActivity,andInducesAntitumorImmunity.MolCancerTher.