GDC-6036-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGDC-6036Cat.No.:HY-145928CASNo.:2417987-45-0分?式:C??H??ClF?N?O?分?量:622.06作?靶點:Ras作?通路:GPCR/GProtein儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(160.76mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.6076mL8.0378mL16.0756mL5mM0.3215mL1.6076mL3.2151mL10mM0.1608mL0.8038mL1.6076mL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:≥2.5mg/mL(4.02mM);Clearsolution1/2MasterofBioactiveMolecules—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:2.5mg/mL(4.02mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.02mM);ClearsolutionBIOLOGICALACTIVITY?物活性GDC-6036?種具有?服?物利?度，選擇性的KRASG12C抑制劑，IC50為<0.01μM。GDC-6036與KRASG12C的開關(guān)II(SW-II)?袋共價結(jié)合，并將其不可逆地鎖定在?活動的GDP結(jié)合狀態(tài)。IC50&TargetK-Ras(G12C)50)體外研究GDC-6036(compound17a)hasanEC50of2nMinK-RasG12C-alkylationHCC1171cells[2]體內(nèi)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