Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECl-amidinehydrochlorideCat.No.:HY-100574ACASNo.:1373232-26-8分?式:C??H??Cl?N?O?分?量:347.24作?靶點(diǎn):ProteinArginineDeiminase;Apoptosis;MicroRNA作?通路:Epigenetics;Apoptosis儲存?式:-20°C,storedundernitrogen,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen,awayfrommoisture)溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(287.99mM;Needultrasonic)H2O:50mg/mL(143.99mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.8799mL14.3993mL28.7985mL5mM0.5760mL2.8799mL5.7597mL10mM0.2880mL1.4399mL2.8799mL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(storedundernitrogen,awayfrommoisture)。-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:≥7.5mg/mL(21.60mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥7.5mg/mL(21.60mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥7.5mg/mL(21.60mM);Clearsolution4.請依序添加每種溶劑：PBSSolubility:5.5mg/mL(15.84mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Cl-amidinehydrochloride?服有效的PAD抑制劑，其對PAD1、PAD3和PAD4的IC50值分別為0.8μM、6.2μM和5.9μM。Cl-amidinehydrochloride可誘導(dǎo)癌細(xì)胞的凋亡。Cl-amidinehydrochloride可誘導(dǎo)miR-16(miRNA-16,microRNA-16)，引起細(xì)胞周期阻滯。Cl-Amidinehydrochloride可阻斷組蛋?3?氨酸化和中性粒細(xì)胞胞外陷阱的形成，并提?敗?癥??的存活率。IC50&TargetIC50:0.8μM(PAD1),5.9μM(PAD4),6.2μM(PAD3)[1][5].體外研究Cl-amidineisabioavailablehaloacetamidine-basedcompoundthatinhibitsalltheactivePADisozymeswithnearequalpotency(kinact/KI=13,000M-1?min-1forPAD4)[1].Cl-amidine(0,5,10,15,20,25,50μg/mL,24hours)inducesapoptosisinTK6lymphoblastoidcellsandHT29coloncancercellsinadose-dependentmanner.Interestingly,thecoloncancercellline(HT29)isrelativelyresistanttoapoptosiscausedbyCl-amidine[2].Cl-Amidinepreventshistone3citrullinationandneutrophilextracellulartrapformation,andimprovessurvivalinamurinesepsismodel[4].ApoptosisAnalysis[2].CellLine:TK6lymphoblastoidcellsandHT29coloncancercells.Concentration:0,5,10,15,20,25,50μg/mL.IncubationTime:24h.Result:Inducedapoptosisdose-dependently.體內(nèi)研究Cl-amidine(75mg/kg,iponcedaily)suppressesandtreatsDSS-inducedcolitisinmice[2].Cl-amidine(5,25,75mg/kg,oralgavage,oncedaily)leadstosignificantreductionsinthehistologyscoresdose-dependently[2].AnimalModel:C57BL/6mice(8-12wkold,DSSmousemodelofcolitis)[2].Dosage:75mg/kg.Administration:IPoncedaily.Result:SuppressedPADactivity,proteincitrullination,andPADlevelsinthecoloninvivo.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:C57BL/6mice(8-12wkold,DSSmousemodelofcolitis)[2].Dosage:5,25,75mg/kg.Administration:Oralgavageoncedaily.Result:Ledtosignificantreductionsinthehistologyscores.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?TranslRes.2022Nov23;S1931-5244(22)00252-3.?CellRep.2021Sep21;36(12):109750.?Neoplasia.2022Nov;33:100835.?FishShellfishImmunol.2022Aug3;S1050-4648(22)00414-4.?ChemResToxicol.2022Feb15.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].YuanLuo,etal.InhibitorsandInactivatorsofProteinArginineDeiminase4:FunctionalandStructuralCharacterization.Biochemistry.2006Oct3;45(39):11727–11736.[2].ChumanevichAA,etal.SuppressionofcolitisinmicebyCl-amidine:anovelpeptidylargininedeiminaseinhibitor.AmJPhysiolGastrointestLiverPhysiol.2011Jun;300(6):G929-38.[3].WitalisonEE,etal.Moleculartargetingofproteinargininedeiminasestosuppresscolitisandpreventcoloncancer.Oncotarget.2015Nov3;6(34):36053-62.[4].BironBM,etal.,Cl-AmidinePreventsHistone3CitrullinationandNeutrophilExtracellularTrapFormation,andImprovesSurvivalinaMurineSepsisModel.JInnateImmun.2017;9(1):22