Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPHPS1Cat.No.:HY-112368CASNo.:314291-83-3分?式:C??H??N?O?S分?量:465.44作?靶點(diǎn):SHP2;Phosphatase作?通路:ProteinTyrosineKinase/RTK;MetabolicEnzyme/Protease儲(chǔ)存?式:-20°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:25mg/mL(53.71mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1485mL10.7425mL21.4850mL5mM0.4297mL2.1485mL4.2970mL10mM0.2149mL1.0743mL2.1485mL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(sealedstorage,awayfrommoisture)。-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?。BIOLOGICALACTIVITY?物活性PHPS1?種有效的選擇性Shp2抑制劑，對(duì)Shp2，Shp2-R362K，Shp1，PTP1B和PTP1B-Q的Ki值分別為0.73，5.8，10.7，5.8和0.47μM[1]。IC50&TargetKi:0.73μM(Shp2),5.8μM(Shp2-R362K),10.7μM(Shp1),5.8μM(PTP1B),0.47μM(PTP1B-Q)[1]體外研究PHPS1(30μM;6days)inhibitsproliferationofhumantumorcells[1].1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEPHPS1(5-20μM;5-360minutes)inhibitsErk1/2butnotAktandStat3phosphorylationinadose-dependentmanner[1].CellViabilityAssay[1]CellLine:HumancancercelllinesMDA-MB-435,HCT-116(coloncarcinoma),HCT-15(coloncarcinoma),PC-3(prostatecarcinoma)HT-29(coloncarcinoma),NCI-H661(lungcarcinoma),andCaki-1(kidneycarcinoma)Concentration:30μMIncubationTime:6daysResult:Resultedinareductionincellnumberofbetween0%(Caki-1)to74%(HT-29).WesternBlotAnalysis[1]CellLine:Madin-Darbycaninekidney(MDCK)cellsConcentration:5,10,20μMIncubationTime:5,15,60,120,360minutesResult:InhibitedHGF/SF(1unit/mL)-inducedphosphorylationandthusactivationofErk1/2overatimeperiodof15minto6h.Incontrast,transientphosphorylationofErk1/2after5minwasnotaffected.ExhibitednoeffectonHGF/SF-inducedactivationofPI3K/AktorStat3.體內(nèi)研究PHPS1(3mg/kg;i.p.injection;everydayduringthelastweekonthehigh-fatdiet)rendersLdlr-/-micelesssusceptibletoatherosclerosisdevelopment[2].AnimalModel:Ldlr-/-(005061)mice[2]Dosage:3mg/kgAdministration:Intraperitoneal(i.p.)injection;everydayduringthelastweekonthehigh-fatdiet.Result:Revealedasignificantdecreaseinatheroscleroticplaquesizeintheaortacomparedwiththeothertwogroups.REFERENCES[1].KlausHellmuth,etal.SpecificInhibitorsoftheProteinTyrosinePhosphataseShp2IdentifiedbyHigh-ThroughputDocking.ProcNatlAcadSciUSA.2008May20;105(20):7275-80.[2].JiaChen,etal.SHP2InhibitorPHPS1ProtectsAgainstAtherosclerosisbyInhibitingSmoothMuscleCellProliferation.BMCCardiovascDisord.2018Apr27;18(1):72.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Producthasnotbeenfullyvalidatedformedic