GDC-0326-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGDC-0326Cat.No.:HY-101272CASNo.:1282514-88-8分⼦式:C₁₉H₂₂N₆O₃分⼦量:382.42作⽤靶点:PI3K作⽤通路:PI3K/Akt/mTOR储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(261.49mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.6149mL13.0746mL26.1493mL5mM0.5230mL2.6149mL5.2299mL10mM0.2615mL1.3075mL2.6149mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(6.54mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.54mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.54mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性GDC-0326有效，选择性的PI3Kα抑制剂，Ki值为0.2nM。IC50&TargetPI3KαPI3KβPI3KδPI3Kγ0.2nM(Ki)26.6nM(Ki)4nM(Ki)10.2nM(Ki)体外研究GDC-0326ishighlyselectiveoverotherkinases.Inapanelof235kinases,onlyoneisinhibitedby>50%byGDC-0326whentestedat1µM.GDC-0326isnotaninhibitorofcytochromeP450enzymestested(IC50>10µMagainst3A4,2C91A2,2C19,2D6),ishighlypermeableinMDCKcellsandhasthermodynamicsolubilityof82µg/mLatpH7.4[1].体内研究GDC-0326ishighlystableinhumanandratlivermicrosomes,andthereisagoodcorrelationwithinvivoratclearance.Itisfoundtohaveconsistentlylowclearanceandhighoralbioavailabilityacrossspeciestested,enablingsignificantsustainedfreedruglevels.DailyadministrationofGDC-0326orallyat0.78,1.56,3.25,6.25,or12.5mg/kgresultsindose-dependentincreaseinTGI(73%,79%,83%,101%,and110%,respectively)andtumorregressions(6PRsoutof10animalat6.25and12.5mg/kg)whencomparedtovehicletreatedmice.DailyadministrationofGDC-0326orallyat0.78,1.56,3.25,6.25,or12.5mg/kgalsoresultsindose-dependentincreaseinTGI(73%,97%,97%,122%,and121%,respectively)intheKPL-4xenograftmodel.Notably,maximumefficacyofGDC-0326isobservedat6.25mg/kgintheKPL-4modelbasedonTGIandtumorregressions(9PRsand1CRoutof10animaltreated)whencomparedtovehicletreatedmice.DosesofGDC-0326upto12.5mg/kgarewelltoleratedbasedonlessthan10%bodyweightloss(datanotshown)[1].PROTOCOLAnimalRats:MaleSprague-Dawleyratsaredosedintravenouslywith1mg/kgofGDC-0326preparedin60%Administration[1]PEG400/10%Ethanol.MaleSprague-DawleyratsaredosedPOwith5mg/kgofGDC-0326in0.5%methylcellulosewith0.2%Tween80(MCT)[1].Mice:FemaleNCRnudemicearedosedintravenouslywith1mg/kgofGDC-0326preparedin60%PEG400/10%EthanolandPOat25mg/kgin0.5%methylcellulosewith0.2%Tween80(MCT)[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].HeffronTP,etal.TheRationalDesignofSelectiveBenzoxazepinInhibitorsoftheα-IsoformofPhosphoinositide3-KinaseCulminating2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEintheIdentificationof(S)-2-((2-(1-Isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yMcePdfHeightCaution:Productha