Lometrexol-hydrate-DDATHF-hydrate-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemELometrexolhydrateCat.No.:HY-14521BCASNo.:1435784-14-7Synonyms:DDATHFhydrate分?式:C??H??N?O?分?量:461.47作?靶點:Antifolate;Apoptosis作?通路:CellCycle/DNADamage;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:40mg/mL(86.68mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1670mL10.8349mL21.6699mL5mM0.4334mL2.1670mL4.3340mL10mM0.2167mL1.0835mL2.1670mL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，并請注意儲備液的保存?式和期限。BIOLOGICALACTIVITY?物活性Lometrexolhydrate(DDATHFhydrate)?種抗嘌呤類抗葉酸(antifolate)藥，可抑制?氨酰胺核糖核苷酸甲酰轉(zhuǎn)移酶(GARFT)的活性，但不會引起可檢測?平的DNA鏈斷裂。Lometrexolhydrate可以進?步抑制嘌呤從頭合成，導致異常的細胞增殖，凋亡(apoptosis)和細胞周期停滯。Lometrexolhydrate具有抗癌活性[1][2]。Lometrexolhydrate還?種有效的?絲氨酸羥甲轉(zhuǎn)移酶1/2(hSHMT1/2)抑制劑[3]。IC50&TargetGARFT[1]1/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemE體外研究Lometrexolhydrate(DDATHFhydrate)bindstightlytoGART,resultinginarapidandprolongeddepletionofintracellularpurineribonucleotides[2].Lometrexolhydrate(1-30μM;2-10hours)inducesrapidandcompletegrowthinhibitioninL1210cells[2].Lometrexolhydrate(1μM;2-24hours)inducescellcyclearrestinmurineleukemiaL1210cells[2].Lometrexolhydrateinducesabnormalproliferationandapoptosisexistinneuraltubedefects(NTDs)[1].CellViabilityAssay[2]CellLine:MouseleukemiaL1210cellsConcentration:1,30μMIncubationTime:2,4,6,8,10hoursResult:Inducedrapidandcompletegrowthinhibition.CellCycleAnalysis[2]CellLine:L1210cellsConcentration:1μMIncubationTime:2,4,8,12,24hoursResult:CausedarapidlossoftheG2/MphasepopulationofcellsandanearlySphaseaccumulationofcellsby8hours.By24h,theSphasepopulationappearedtobeslowlyshiftingtohigherDNAcontent,andhence,frommid-to-lateSphase.體內(nèi)研究Lometrexolhydrate(DDATHFhydrate;i.p.;15-60mg/kg;ongestationday7.5)increasestherateofembryonicresorptionandgrowthretardationinadose-dependentmanner[1].Lometrexolhydrate(i.p.;40mg/kg)maximallyinhibitsGARFTactivityafterat6hoursandthereaftergraduallyincreaseswithtimebutremainssignificantlylowerthancontrolevenat96hours.LevelsofATP,GTP,dATPanddGTPofNTDsembryonicbraintissuedecreasessignificantlyat6h,andmoresignificantlyovertime[1].AnimalModel:C57BL/6mice(7-8week,18-20g)[1]Dosage:15,30,35,40,45and60mg/kgAdministration:Intraperitonealinjection;ongestationday7.5Result:Increasedtherateofembryonicresorptionandgrowthretardationinadose-dependentmanner.REFERENCES[1].XuL,etal.Theeffectofinhibitingglycinamideribonucleotideformyltransferaseonthedevelopmentofneuraltubeinmice.NutrMetab2/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemE(Lond).2016Aug23;13(1):56.[2].JulieLBronder,etal.AntifolatesTargetingPurineSynthesisAllowEntryofTumorCellsIntoSPhaseRegardlessofp53Function.CancerRes.2002Sep15;62(18):5236-41.[3].Emma