Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETrimetrexatetrihydrochlorideCat.No.:HY-10373ACASNo.:1658520-97-8Synonyms:CI-898trihydrochloride分?式:C??H??Cl?N?O?分?量:478.8作?靶點(diǎn):Dihydrofolatereductase(DHFR);Antibiotic;Antifolate;Parasite;Bacterial;DNA/RNASynthesis作?通路:MetabolicEnzyme/Protease;Anti-infection;CellCycle/DNADamage儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Trimetrexate(CI-898)trihydrochloride?種抗?素(antibiotic)，也?種有效的、具有?服活性的?氫葉酸還原酶(DHFR)抑制劑，減少DNA和RNA前體的產(chǎn)?并導(dǎo)致細(xì)胞死亡，對(duì)?DHFR和剛地?形?(Toxoplasmagondii)DHFR的IC50分別為4.74nM和1.35nM。Trimetrexatetrihydrochloride也能抑制多種癌細(xì)胞的?長。Trimetrexatetrihydrochloride可?于卡?肺孢??肺炎(PCP)和癌癥的研究。IC50&TargetToxoplasmagondii體外研究Trimetrexatetrihydrochloride(0.1μM,18h)completelyinhibitsproliferationoftoxoplasmainmurinemacrophages[3].Trimetrexatetrihydrochloride(1μM)cancrossthetoxoplasmacellmembraneandrapidlyreacheshighintracellularconcentrations(108pmol/107cellswithin10min)[3].Trimetrexate(0.1mM;24h)inhibitscellgrowthby50-60%inSNU-C4andNCI-H630celllines[5].Trimetrexate(1and10mM;24h)produceslethalityandinhibitsDHFRinC4cells[5].CellProliferationAssay[5]CellLine:SNU-C4andNCI-H630Concentration:0.1mMIncubationTime:24h1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:Inhibitedcellgrowthby50-60%inbothcelllines.CellProliferationAssay[5]CellLine:C4cellsConcentration:1and10mMIncubationTime:24hResult:Produced42%and50%lethalityat1and10mM,respectively.體內(nèi)研究Trimetrexate(180mg/kgor30mg/kg;p.o.ori.p.;daily)trihydrochlorideextendsthemediansurvivalofthetoxoplasmainfectedmiceandshowsantitoxoplasmaactivity[3].Trimetrexate(0-30mg/kg;i.v.;oncedailyfor5days)trihydrochlorideshowschronictoxicityinrats[4].AnimalModel:ToxoplasmainfectedfemaleBALB/cmiceweighingabout20g[3]Dosage:180mg/kgor30mg/kgAdministration:180mg/kgperdayorallyinthedrinkingwateror30mg/kgperdayi.p.Result:Extendedthemediansurvivaloftheinfectedmiceto10d(p.o.)or19d(i.p.).AnimalModel:CharlesRiverWistarCrl(WI)BRratsweighingapproximately150to200g[4]Dosage:0,1,10,or30mg/kgAdministration:Intravenousinjection,oncedailyfor5consecutivedaysfollowedbya23-dayrecoveryperiodResult:Showedchronictoxicity,thetesticularchangespersistingduringthecourseofmultiplecyclesofdosingwerenotreversiblewithin21days,butrequiredanadditional56daysforessentiallycompleterecovery.REFERENCES[1].HopperAT,etal.DiscoveryofSelectiveToxoplasmagondiiDihydrofolateReductaseInhibitorsfortheTreatmentofToxoplasmosis.JMedChem.2019Feb14;62(3):1562-1576.[2].Fulton,B.,etal.Trimetrexate.Drugs49,563–576(1995).[3].AllegraCJ,etal.Potentinvitroandinvivoantitoxoplasmaactivityofthelipid-solubleantifolatetrimetrexate.JClinInvest.1987Feb;79(2):478-82.[4].DethloffLA,etal.Chronictoxicityoftheanticanceragenttrimetrexateinrats.FundamApplToxicol.1992Jul;19(1):6-14.[5].GremJL,VoellerDM,GeoffroyF,HorakE,JohnstonPG,AllegraCJ.Determinantsoftrimetrexatelethalityinhumancoloncancercells.BrJCancer.1994Dec;70(6):1075-84.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMcePdfHeightCaution:Producthasnotbe