IACS-13909-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEIACS-13909Cat.No.:HY-137092CASNo.:2160546-07-4分?式:C??H??Cl?N?分?量:377.27作?靶點(diǎn):Phosphatase作?通路:MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:10mg/mL(26.51mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.6506mL13.2531mL26.5062mL5mM0.5301mL2.6506mL5.3012mL10mM0.2651mL1.3253mL2.6506mL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%salineSolubility:≥1mg/mL(2.65mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性IACS-13909?種有效的選擇性的，具有?服活性的SHP2變構(gòu)抑制劑，其IC50為15.7nM，Kd為32nM。與其他磷酸酶(包括SHP1)相?，IACS-13909對SHP2的選擇性更?。IACS-13909抑制受體酪氨酸激酶(RTK)/MAPK途徑的信號傳導(dǎo)，并具有抗癌作?。IC50&TargetIC50:15.7nM(SHP2)[1]Kd:32nM(SHP2)[1]體外研究IACS-13909(10nM-10μM;14days)treatmentpotentlysuppressestheproliferationofwild-typeSHP2andKYSE-520cells[1].IACS-13909(1-5μM;2hours)treatmentpotentlysuppressespERKandpMEKlevelsinwild-typeSHP2andKYSE-520cells[1].IACS-13909potentlysuppressestheproliferationofboththeparentalcellsandNCI-H1975CScellsinadose-dependentmanner,withsimilarpotency(GI50~1μM).IACS-13909(0.041-3.3μM)suppressespERKinNCI-H1975CScellsinadose-dependentmanner[1].CellProliferationAssay[1]CellLine:Wild-typeSHP2andKYSE-520cellsConcentration:10nM,100nM,1μM,10μMIncubationTime:14daysResult:Potentlysuppressedthecellproliferation.WesternBlotAnalysis[1]CellLine:Wild-typeSHP2andKYSE-520cellsConcentration:1μM,5μMIncubationTime:2hoursResult:PotentlysuppressedpERKandpMEKlevels.體內(nèi)研究IACS-13909(70mg/kg;oraladministration;daily;for21days)treatmentpotentlysuppressestumorgrowthinmice,with100%tumorgrowthinhibition(TGI)observedfollowing21daysofdosing[1].AnimalModel:NSGmice(20-28g)injectedwithKYSE-520cells[1]Dosage:70mg/kgAdministration:Oraladministration;daily;for21days2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:Potentlysuppressedtumorgrowthinmice.REFERENCES[1].YutingSun,etal.AllostericSHP2Inhibitor,IACS-13909,OvercomesEGFR-DependentandEGFR-IndependentResistanceMechanismstowardOsimertinib.CancerRes.2020Nov1;80(21):4840-4853.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalappl