FA16-DataSheet-生命科學試劑-MCE

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEFA16Cat.No.:HY-151964分?式:C??H??F?N?O?S分?量:466.52作?靶點:Ferroptosis作?通路:Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性FA16?種特異、代謝穩(wěn)定的鐵死亡(ferroptosis)誘導劑(IC50=1.26μM;HT1080cells)，2-(三氟甲)苯并咪唑的衍?物。胱氨酸/?氨酸反轉(zhuǎn)運蛋?(systemXc-)介導了細胞內(nèi)?氨酸和細胞外胱氨酸的交換，F(xiàn)A16通過抑制systemXc-?使功能。FA16也能夠在HepG2異種移植瘤模型中顯著抑制腫瘤?長。體外研究FA16(1μM;5min)hassatisfactorymetabolicstabilityinratandhumanlivermicrosomes[1].FA16(5μM;10h)induceslipidROSaccumulationandinhibitsglutamatereleasedose-dependentlyinHT1080cells[1].FA16(5μM;24h)resultsmitochondriashrunkenwithincreasedmembranedensity,whichwasinlinewiththemorphologicalfeaturerelatedtoferroptosis[1].FA16(10μM;24h)inducedcelldeath,whichcanberescuedbytheferroptosisinhibitorsFer-1,TroloxorDFO,butnotbytheinhibitorsofapoptosisornecroptosis[1].ParameterMicrosomalstability(T1/2min)Intrinsicclearance(μL/min/mgprotein)Human15.688.6Rat10.4132.8CellViabilityAssay[1]CellLine:Humancancercelllines:Clear-cellrenalcellcarcinomacells(786-O),breastcancercells(MDA-MB-231),cervicalcancercells(HeLa),hepatocellularcarcinomacells(HepG2),melanomacells(A375),andprostatecancercells(DU145);Humannormalcelllines:cardiomyocytes(AC16),colonmucosalepithelialcells(NCM460),embryonickidneycells(293T),andhepaticcells(LO2)Concentration:0-10μM1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:48hoursResult:InhibitedcellgrowthwithIC50sof0.7μM(786-O),4.34μM(MDA-MB-231),1.91μM(HeLa),1.33μM(HepG2),2.31μM(A375),and1.64μM(DU145),respectively.Immunofluorescence[1]CellLine:HT1080cellsConcentration:5μMIncubationTime:10hoursResult:SignificantlyinducedlipidROSaccumulation,asindicatedbythegreatenhancementingreenfluorescenceintensity.RT-PCR[1]CellLine:HT1080cellsConcentration:0.5μM,1μM,and5μMIncubationTime:6hoursand18hoursResult:IncreasedthesystemXc-componentSLC7A11,ChaCGSHspecificγ-glutamylcyclotransferase1(CHAC1),butlittlechangedGPX4.體內(nèi)研究FA16(15or30mg/kg;i.p.;everyotherfor21d)significantlyinhibitstumorgrowthwithgoodsafety(noweightloss)in786-Oxenograftmicemodel,anditinducedferroptosisintumortissues[1].AnimalModel:BALB/cnudemicebearingHepG2tumors(s.c.)[1]Dosage:15or30mg/kgAdministration:Intraperitonealinjection;everyotherfor21daysResult:Significantlyinhibitedtumorgrowthwithatumorgrowthinhibition(TGI)valueof47.6%and77.1%at15and30mg/kg,respectively.REFERENCES[1].FangY,etal.Discoveryandoptimizationof2-(trifluoromethyl)benzimidazolederivativesasnovelferroptosisinducersinvitroandinvivo.EurJMedChem.2023Jan5;245(Pt1):114905.McePdfHeightCaution:Producthasnotbeenfullyvalidatedforme