K-975-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEK-975Cat.No.:HY-138565CASNo.:2563855-03-6分?式:C??H??ClNO?分?量:287.74作?靶點:YAP作?通路:StemCell/Wnt儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:220mg/mL(764.58mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.4754mL17.3768mL34.7536mL5mM0.6951mL3.4754mL6.9507mL10mM0.3475mL1.7377mL3.4754mL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?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據(jù)您的實驗動物和給藥?式選擇適當?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：(為保證實驗結果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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:5.5mg/mL(19.11mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥5.5mg/mL(19.11mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥5.5mg/mL(19.11mM);ClearsolutionBIOLOGICALACTIVITY?物活性K-975?種有效的，具有選擇性和?服活性的TEAD抑制劑，可強烈抑制YAP1/TAZ和TEAD之間的蛋?質-蛋?質相互作?。K-975通過丙烯酰胺結構與位于TEAD棕櫚酸酯結合?袋中的Cys359共價結合。K-975具有抗惡性胸膜間?瘤的活性。IC50&TargetTEAD[1]體外研究K-975(0.1-10000nM;144h)inhibitsthecellproliferationofNF2-non-expressingmalignantpleuralmesothelioma(MPM)celllines[1].K-975(10-10000nM;24h)inhibitsprotein-proteininteraction(PPI)betweenHalo-YAPandendogenousTEAD1/4andHalo-TAZandTEAD1/4inNCI-H226cells[1].K-975(0.1-10000nM;24h)stronglyinhibitsthereporteractivityinNCI-H661/CTGF-Luccells,withthemaximuminhibitionof~70%,anddoesnotinhibitthereporteractivityinNCI-H661/NRF2-Luccells[1].K-975(1-10000nM;24h)decreasestheexpressionsofCTGF,IGFBP3,andNPPBmRNAs,andincreasestheexpressionofFBXO32mRNAinNCI-H226cells[1].CellProliferationAssay[1]CellLine:NF2-non-expressingMPMandNF2-expressingmalignantMPMcellsConcentration:0.1,1,10,100,1000,10000nMIncubationTime:144hoursResult:HadastrongerinhibitoryeffectagainstNF2-non-expressingcelllinesthanNF2-expressingcelllines.InhibitedtheproliferationofMSTO-211Hcells,anNF2-expressingcellline.WesternBlotAnalysis[1]CellLine:NCI-H226cellsConcentration:10,100,1000,10000nMIncubationTime:24hoursResult:InhibitedTEAD1-YAP1PPIandTEAD4-YAP1PPI.InhibitedTEAD1-TAZPPIandTEAD4-TAZPPI.體內研究K-975(10-300mg/kg;p.o.twiceadayfor14days)inhibitsthetumorgrowthbyinhibitingYAP1/TAZ-TEAD2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEsignalinginMPMxenograftmousemodels[1].AnimalModel:MaleSCIDmice(5weeks)injectedwithNCI-H226orMSTO-211Hcells[1]Dosage:10,30,100,300mg/kgAdministration:P.o.twiceadayfor14daysResult:Exhibitedstronganti-tumoreffectinMPMs.c.xenograftmousemodels.DecreasedtheexpressionsofCTGF,IGFBP3,andNPPB,andincreasedtheexpressionofFBXO32intheNCI-H226xenograftmodel.REFERENCES[1].KanedaA,et,al.ThenovelpotentTEADinhibitor,K-975,inhibitsYAP1/TAZ-TEADprotein-proteininteractionsandexertsananti-tumoreffectonmalignantpleuralmesothelioma.AmJCancerRes.2020Dec1;10(12):4399-4415.McePdfHeightCaution:Producthasnotbeen