GC-072-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGC-072Cat.No.:HY-178738CASNo.:1371629-36-5分⼦式:C₂₀H₁₆F₂N₂O₃分⼦量:370.35作⽤靶点:Antibiotic;Bacterial;Topoisomerase;DNA/RNASynthesis作⽤通路:Anti-infection;CellCycle/DNADamage储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性GC-072⼀种⼝服有效的4-氧代喹啉抗⽣素(antibiotic)，选择性地抑制细DNA回旋酶(bacterialDNAgyrase)和拓扑异构酶IV(TopoIV)酶。GC-072不抑制⼈拓扑异构酶I和II。GC-072对多种细株，包括⾰兰⽒阳性、⾰兰⽒性和耐药，均表现出强效抗活性。GC-072对类⿐伯克霍尔德(Burkholderiapseudomallei)也显⽰出细胞外和细胞内的杀活性。在露于致死性吸⼊性类⿐伯克霍尔德感染模型的⼩⿏中，GC-072可剂量依赖性地提⾼⼩⿏存活率。GC-072可⽤于研究类⿐病[1]。IC50&TargetDNAGyraseTOPOIVDNAGyraseTOPOIV2μM(IC50,S.aureus)4-30μM(IC50,S.0.18-1.5μM(IC50,4.22-8.45μM(IC50,aureus)E.coli)E.coli)体外研究GC-072(0.25μg/mL,2.5μg/mL;0,1,5,24hours)effectivelyinhibitsthegrowthofintracellularB.pseudomalleiinmurinemacrophagecellsinarapidtime-anddose-dependentmanner,withnoviablebacteriadetectableafter24hoursateitherconcentration[1].GC-072inhibitsbothE.coliandS.aureusgyraseandTopoIV.TheIC50valuesof2μM,0.18-1.50μM,4-30μM,and4.22-8.45μMforS.aureusgyrase,E.coligyrase,S.aureusTopoIV,andE.coliTopoIV,respectively[1].GC-072demonstratesgoodactivityagainstB.pseudomallei,withanMIC90of0.25ꢀμg/mLandarangeof≤0.008to1ꢀμg/mL[1].TheMIC90sofGC-072againstB.anthracis,Y.pestis,F.tularensis,andB.malleiare0.002ꢀμg/mL,0.015ꢀμg/mL,≤0.0005ꢀμg/mL,and0.12ꢀμg/mL,respectively[1].GC-072isfullyactiveagainstthepanelofdrug-resistantB.pseudomalleistrainstested(i.e.,Ceftazidime(HY-B0593)-,Clavulanate(HY-A0256A)-andTrimethoprim(HY-B0510)-resistantstrains)[1].1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体内研究GC-072(1-30mg/kg;oral(gavage);q8h;14days)andGC-072(37.5-150mg/kg;oral(gavage);q8h;14days)improvesurvivalinpneumonicmodelofmelioidosis(infectedwithB.pseudomalleistrain1026bviaaerosolchallenge)[1].AnimalModel:BALB/c(Female,6to8weeks,19.75g)(infectedwithB.pseudomalleistrain1026bviaaerosolchallenge)[1]Dosage:1mg/kg,3mg/kg,10mg/kg,30mg/kgAdministration:oral(gavage);1,3,10,30mg/kg;q8h;14daysResult:Whentreatmentwasinitiated8ꢀhpostchallenge,0%,0%,70%,and90%survivalwasobservedinmiceadministered1,3,10,and30ꢀmg/kg,respectively.Whentreatmentwasinitiated16ꢀhpostchallenge,50%and100%survivalwasobservedinthe10and30ꢀmg/kggroups,respectively.AnimalModel:BALB/c(Female,6to8weeks,19.75g)(infectedwithB.pseudomalleistrain1026bviaaerosolchallenge)[1]Dosage:37.5mg/kg,75mg/kg,150mg/kgAdministration:oral(gavage);37.5,75,150mg/kg;q8h;14daysResult:Wheninitiated8ꢀhpostexposure,miceinthe37.5-,75-,and150-mg/kgtreatmentgroupsdemonstrated90%,90%,and80%survival,respectively.Inthe24-htreatmentinitiationgroups,overallsurvivalwaslow.However,eachdoseprovidedasignificantsurvivaladvantagecomparedtovehiclecontrol.REFERENCES[1].ShearerJD,etal.GC-072:ANovelTherapeuticCandidateforOralTreatmentofMelioidosisandInfectionsCausedbySelectBiothreatPathogens.AntimicrobAgentsChemother.2019;63(12):e00834-19.McePdfHeightCaution:Producthasnotbeenfu