Conteltinib-CT-707-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEConteltinibCat.No.:HY-109084CASNo.:1384860-29-0Synonyms:CT-707分?式:C??H??N?O?S分?量:635.82作?靶點(diǎn):FAK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:31.25mg/mL(49.15mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.5728mL7.8639mL15.7277mL5mM0.3146mL1.5728mL3.1455mL10mM0.1573mL0.7864mL1.5728mL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%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(3.27mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.27mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.27mM);ClearsolutionBIOLOGICALACTIVITY?物活性Conteltinib(CT-707)?種多激酶抑制劑，可靶向作?于FAK，ALK和Pyk2。Conteltinib(CT-707)對(duì)FAK具有顯的抑制作?，IC50為1.6nM[1]。IC50&TargetIC50:1.6nM(FAK)[1]體外研究Conteltinib(CT-707)synergizeswithXL184tosuppresshepatocellularcarcinomabyblockingXL184-inducedFAKactivation[1].ThecombinationofXL184(5μM)andConteltinib(3μM)significantlyreducesthesurvivalfraction,comparedwitheachagentalone[1].ThecombinationofXL184(5μM)andConteltinib(3μM)resultsinenhancedcaspase-dependentapoptosisinhumanhepatocellularcarcinomacelllines[1].TheFAKphosphorylationinducedbyXL184(5μM)mightbeinvolvedinthesynergisticantitumoreffectofConteltinib(3μM)andXL184[1].CellViabilityAssay[1]CellLine:ThehumanhepatocellularcarcinomacelllinesHepG2andBel-7402Concentration:1.0,1.5,2.0,2.5,and3.0μMforHepG2cells;0.2,0.4,0.8,1.5,and3.0μMforBel-7402cellsIncubationTime:72hoursResult:WhencellswereexposedtoXL184(5μM),Conteltinib(3μM),ortheircombination,thesurvivalrateswere57.3%,39.3%,and11.2%,respectively,inHepG2;thoseinBel-7402were57.8%,61.6%,and34.2%,respectively.ApoptosisAnalysis[1]CellLine:HepG2andBel-7402cellsConcentration:3μMIncubationTime:48hoursResult:Theapoptosisratesofcontrol,XL184,Conteltinib,andcombinationgroupsinHepG2were5.0%,10.5%,18.4%,and41.1%,respectively,andthoseinBel-7402were4.4%,16.3%,8.7%,and36.4%,respectively.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEWesternBlotAnalysis[1]CellLine:HepG2andBel-7402Concentration:3μMIncubationTime:24hoursResult:CouldmarkedlydecreaseFAKphosphorylationinducedbyXL184,whichmightpartiallyaccountforthesynergeticeffect.體內(nèi)研究ThecombinationofXL184(20mg/kgoncedailyforfirst3days;i.g.10mg/kgonceadayfor4thday;noadministrationfrom5thto10thdays;i.g.10mg/kgonceadayfromthe10thto14thdays)andCT-707(i.g.50mg/kgtwiceadayforfirst3days,7th,8th,11th,12th,and14thdays;onceadayfor4th,6th,9th,10th,and13thdays;noadministrationforthe5thday)showsthesynergisticantitumoreffectinHepG2xenograftnudemice[1].AnimalModel:NudemicetransplantedwithHepG2xenografts[1]Dosage:50mg/kgAdministration:Intragastrically(i.g.)twiceadayforfirst3days,7th,8th,11th,12th,and14thdays;onceadayfor4th,6th,9th,10th,and13thdays;noadministrationforthe5thday.Result:Causedamoderatedecreaseintherelativetumorvolume(RTV).Theinhibitionrateofcombinationgroupreached77.4%,whereasthemono-treatmentofXL184orCT-707alonecaused30.7%and19.4%inhibitioninthetumorweight,respectively.REFERENCES[1].WangDD,etal.CT-707,aNovelFAKInhibitor,SynergizeswithXL184toSuppressHepatocellularCarcinomabyBlockingXL184-InducedFAKActivation.MolCancerTher.2016Dec;15(12):2916-2925.McePd