SHP099-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESHP099hydrochlorideCat.No.:HY-100388ACASNo.:2200214-93-1分⼦式:C₁₆H₂₀Cl₃N₅分⼦量:388.72作⽤靶点:SHP2;Phosphatase作⽤通路:ProteinTyrosineKinase/RTK;MetabolicEnzyme/Protease储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:4.1mg/mL(10.55mM;Needultrasonicandwarming)H2O:≥2.5mg/mL(6.43mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5725mL12.8627mL25.7255mL5mM0.5145mL2.5725mL5.1451mL10mM0.2573mL1.2863mL2.5725mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.43mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：50%PEG300>>50%salineSolubility:20mg/mL(51.45mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性SHP099hydrochloride有效，选择性，有⼝服活性的SHP2抑制剂，IC50值为70nM。IC50&TargetIC50:70nM(SHP2)[1]体外研究TheX-rayco-crystalforSHP099withSHP2revealsanewinteractionwiththebasicamineandthePhe113backbonecarbonyl.SHP099showsinhibitionofcellproliferation(KYSE-520model)withanIC50of1.4μM.SHP099showshighsolubilityandhighpermeabilitywithnoapparenteffluxinCaco-2cells[1].SHP099concurrentlybindstotheinterfaceoftheN-terminalSH2,C-terminalSH2,andproteintyrosinephosphatasedomains,thusinhibitingSHP2activitythroughanallostericmechanism.SHP099suppressesRAS–ERKsignallingtoinhibittheproliferationofreceptor-tyrosine-kinase-drivenhumancancercells[2].体内研究Afterasingledosesof30and100mg/kg(redandbluelines,respectively),dose-dependentexposureandmodulationofthepharmacodynamicmarkerp-ERKisobservedinthexenografts.Adailyoraldoseof10or30mg/kgyield19%and61%tumorgrowthinhibition,respectively.Tumorstasisisachievedat100mg/kg[1].PROTOCOLKinaseAssay[1]TheinhibitionofSHP2fromthetestedcompounds(SHP099)concentrationsvaryingfrom0.003-100μMismonitoredusinganassayinwhich0.5nMofSHP2isincubatedwithof0.5μMofpeptideIRS1_pY1172(dPEG8)pY1222.After30-60minutesincubationatthesurrogatesubstrate,DiFMUPisaddedtothereactionandincubatedat25°Cfor30minutes.Thereactionisthenquenchedbytheadditionof5μLofa160μMsolutionofbpV(Phen).Thefluorescencesignalismonitoredusingamicroplatereaderusingexcitationandemissionwavelengthsof340nmand450nm,respectively[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]Cellsareplatedonto96-wellplatesin100μLmedium.SHP099withvariousconcentrations(1.25,2.5,5,10,20μM)areadded24haftercellplating.Atday5,50μLCelltiter-Gloreagentisadded,andtheluminescentsignalisdetermined[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CancerDiscov.2018Oct;8(10):1237-1249.•SignalTransductTargetTher.2022Sep12;7(1):317.•NatImmunol.2021Oct22.•MolCell.2021Oct7;81(19):4076-4090.e8.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•NatCommun.2018Oct30;9(1):4507.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].GarciaFortanetJ,etal.AllostericInhibitionofSHP2:IdentificationofaPotent,Selective,andOrallyEfficaciousPhosphataseInhibitor.JMedChem.2016Sep8;59(17):7773-82.[2].ChenYN,etal.AllostericinhibitionofSHP2phosphataseinhibitscancersdrivenbyreceptortyrosinekinases.Nature.2016Jul7;535(7610):148-52.[3].CarmineFedele,etal.SHP2InhibitionAbrogatesMEKinhibitorResistanceinMultipleCancerModels.bioRxiv.April25,2018.