GDC-6036-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGDC-6036Cat.No.:HY-145928CASNo.:2417987-45-0分⼦式:C₂₉H₃₂ClF₄N₇O₂分⼦量:622.06作⽤靶点:Ras作⽤通路:GPCR/GProtein储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(160.76mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6076mL8.0378mL16.0756mL5mM0.3215mL1.6076mL3.2151mL10mM0.1608mL0.8038mL1.6076mL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。-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(4.02mM);Clearsolution1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(4.02mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.02mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性GDC-6036⼀种具有⼝服⽣物利⽤度，选择性的KRASG12C抑制剂，IC50为<0.01μM。GDC-6036与KRASG12C的开关II(SW-II)⼝袋共价结合，并将其不可逆地锁定在⾮活动的GDP结合状态。IC50&TargetK-Ras(G12C)50)体外研究GDC-6036(compound17a)hasanEC50of2nMinK-RasG12C-alkylationHCC1171cells[2]体内研究GDC-6036(10-100mg/kg/day;POfor7days)decreasestheratiooffreeKRASG12C[1].AnimalModel:FemaleC.B-17SCID(Inbred)mice(20-21weeksold;24.1g)withhumanNSCLCNCI-H2030.X1.1cells[1]Dosage:10,25,or100mg/kgAdministration:Oralgavage(PO)everyday(QD)for7days(vehicle:0.5%methylcellulose)Result:DecreasedtheratiooffreeKRASG12Ctointernalstandard.Dose-dependenttargetengagementwasobservedforalltimepoints(2,8,and24hpost-lastdose),withover90%KRASG12Cengagementobservedforthehighestdose100mg/kgassessed.REFERENCES[1].LingyaoMeng,etal.AssessmentofKRASG12CTargetEngagementbyaCovalentInhibitorinTumorBiopsiesUsinganUltra-SensitiveImmunoaffinity2D-LC-MS/MSApproach.AnalChem.2022Sep20;94(37):12927-12933.[2].SushantMalhotra,etal.Fusedringcompounds.WO2020097537A2.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearch