MRTX0902-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMRTX0902Cat.No.:HY-145926CASNo.:2654743-22-1分⼦式:C₂₂H₂₄N₆O分⼦量:388.47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:12.5mg/mL(32.18mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5742mL12.8710mL25.7420mL5mM0.5148mL2.5742mL5.1484mL10mM0.2574mL1.2871mL2.5742mL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>>90%(20%SBE-β-CDinsaline)Solubility:≥1.25mg/mL(3.22mM);Clearsolution1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性MRTX0902⼀种⼝服有效的SOS1的抑制剂，IC50为46nM[1]。IC50&TargetKRAS-SOS146nM(IC50)体外研究MRTX0902(compound32)(1μM;0,2,4,8,15,and30minutes)showsamoderateClintvalueof195mL/min/kginhumanlivermicrosomeandalowlipophilicitywithcLogPof3.4[1].MRTX0902displayshighselectivityonSOS1(Ki=2nM)overSOS2andEGFR(bothKivalues>10,000nM),MRTX0902inhibitsMKN1cellswithanIC50valueof29nM[1].体内研究MRTX0902(compound32)(25,50mg/kg;p.o.;twicedaily;25d)showsanti-tumoreffectinmousemodelandresultstumorregression[1].MRTX0902(1-3mg/kgfori.v.or10-30mg/kgforp.o.;singledose)exhibitsgoodbrainpenetrance,lowclearance,andhighbioavailability[1].PKParametersforMRTX0902acrossSpecies[1]ParameterRouteDose(mg/kg)Cl(mL/min/kg)Vd,ss(L/kg)T1/2(iv)(h)F(%)MouseIV/PO3/304.40.281.369RatIV/PO1/1014.60.280.6283DogIV/PO2/107.60.480.8638AnimalModel:FemaleCD-1mice[1]Dosage:50mg/kgAdministration:Oralgavage;twicedaily;1dayResult:ResultedfreedrugexposureinthebrainaswellastheeffluxratiointheCaco-2assay(ER=1.5).Showedshorthalf-lifeofthecompoundinmice(T1/2=1.3h).AnimalModel:MIAPaCa-2xenograftmodelinmouse[1]Dosage:25mg/kg;50mg/kgAdministration:Oralgavage;twicedaily;25daysResult:Reducedtumorgrowthby41%and53%at25mg/kgand50mg/kgadministration.REFERENCES[1].KetchamJM,etal.DesignandDiscoveryofMRTX0902,aPotent,Selective,Brain-Penetrant,andOrallyBioavailableInhibitoroftheSOS1:KRASProtein-ProteinInteraction.JMedChem.2022Jul28;65(14):9678-9690.McePdfHeight2/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECaution:Producthasnotbeenfullyvalidatedformedicalapplicat