GGTI-2418-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGGTI-2418Cat.No.:HY-16231CASNo.:501010-06-6分?式:C??H??N?O?分?量:441.52作?靶點:ROSKinase;Apoptosis作?通路:ProteinTyrosineKinase/RTK;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:125mg/mL(283.11mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2649mL11.3245mL22.6490mL5mM0.4530mL2.2649mL4.5298mL10mM0.2265mL1.1325mL2.2649mL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:≥2.08mg/mL(4.71mM);Clearsolution1/3MasterofBioactiveMolecules—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:≥2.08mg/mL(4.71mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.71mM);ClearsolutionBIOLOGICALACTIVITY?物活性GGTI-2418?種?效，競爭性和選擇性的?葉?葉轉(zhuǎn)移酶I(GGTaseI)抑制劑。GGTI-2418抑制GGTaseI和FTase活性，IC50分別為9.5nM和53μM。GGTI-2418還增強p27(Kip1)并誘導(dǎo)乳腺腫瘤顯消退[1]。IC50&TargetIC50:9.5nM(GGTaseI),53μM(FTase)[1]體外研究GGTI-2418inhibitsGGTaseIandFTaseactivitieswithIC50sof9.5±2.0nMand53±11μM,respectively,a5,600-foldselectivitytowardinhibitionofGGTaseIversusFTase.GGTI-2418demonstratescompetitiveinhibitionofGGTaseIagainsttheH-Ras-CVLLproteinwithaKiof4.4±1.6nM[1].GGTi-2418(10-15μM;16hours)treatmentdelocalizesFBXL2andstabilizesIP3R3[2].WesternBlotAnalysis[2]CellLine:HeLacellsConcentration:10-15μMIncubationTime:16hoursResult:DelocalizedFBXL2andstabilizedIP3R3.體內(nèi)研究GGTI-2418(100mg/kgdailyor200mg/kgeverythirdday;15days)significantlyinhibitsthegrowthofbreasttumorxenograftsinnudemicewithMDA-MB-231xenografts[1].GGTI-2418(100mg/kgdaily;5days)inducesregressionofErbB2-drivenmammarytumorsinErbB2transgenicmice[1].GGTI-2418inhibitsthegeranylgeranylationofRap1andcausesadramaticdecreaseinS473phosphorylationofAkt.GGTI-2418alsoupregulatesp27levelsinvivo[1].AnimalModel:NudemiceimplantedwithMDA-MB-231breastcancertumors[1]Dosage:100mg/kgdailyor200mg/kgeverythirddayAdministration:Injectedintraperitoneally;15daysResult:Inhibitedthegrowthofbreasttumorxenografts.AnimalModel:ErbB2transgenicmice[1]Dosage:100mg/kg/day2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration:Subcutaneously;5daysResult:Haltedtumorgrowthandinducedmassivetumorregression.Tumordecreasedby76%followingGGTI-2418treatment.REFERENCES[1].KaziA,etal.BlockadeofproteingeranylgeranylationinhibitsCdk2-dependentp27Kip1phosphorylationonThr187andaccumulatesp27Kip1inthenucleus:implicationsforbreastcancertherapy.MolCellBiol.2009Apr;29(8):2254-63.[2].KuchayS,etal.PTENcounteractsFBXL2topromoteIP3R3-andCa-mediatedapoptosislimitingtumourgrowth.Nature.2017Jun22;546(7659):554-558.McePdfHeightCaution:Producthasnotbeenfull