Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETES-1025Cat.No.:HY-111365CASNo.:1883602-21-8分?式:C??H??N?O?S?分?量:383.44作?靶點:Others作?通路:Others儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:100mg/mL(260.80mM;Needwarming)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.6080mL13.0399mL26.0797mL5mM0.5216mL2.6080mL5.2159mL10mM0.2608mL1.3040mL2.6080mL請根據產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，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?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：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；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沉淀、析出現象，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:≥2.5mg/mL(6.52mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.52mM);ClearsolutionBIOLOGICALACTIVITY?物活性TES-1025?種有效的和選擇性?α-氨-β-羧粘康酸-ε-半醛脫羧酶(ACMSD)抑制劑，IC50為13nM[1]。IC50&TargetIC50:13±3nM(humanACMSD)[1]體外研究TES-1025isalownanomolarhumanACMSDinhibitor,whichincreasesNAD+levelsincellularsystems[1].體內研究TES-1025issubjectedtoinvivopharmacokineticstudies,followingintravenous(IV)andoral(PO)dosingsofmaleCD-1mice.Aftertheintravenousadministrationof0.5mg/kg,TES-1025showslowbloodclearance,withlowvolumesofdistributionandhalf-lives(t1/2)ofabout5.33h,althoughafteroraladministrationat5mg/kg,thebloodconcentrationofTES-1025isquantifiableforupto8h.AgoodsystemicexposureisrecordedforTES-1025,withaCmaxof2570ng/mLreachesat2hafterdosing.ThegreateroralexposureofTES-1025isfurtherconfirmedintheliverandkidneyswithAUC0-8hof19?200h?ng/mLand36?600h?ng/mL,respectively[1].PROTOCOLKinaseAssay[1]RecombinanthACMSDisexpressedinPichiapastorisandpurified.Itsenzymeactivityisassayedbyacoupledspectrophotometricassay.Briefly,inapre-assaymixture,theACMSsubstrateisgeneratedfrom10μM3-hydroxyanthranilicacidbyrecombinant3-hydroxyanthranilate3,4-dioxigenasefromRalstoniametallidurans.ACMSformationismonitoredat360nm,andafterthereactioniscomplete,anappropriateamountofACMSDisadded.ActivityiscalculatedfromtheinitialrateoftheabsorbancedecreasesubtractedfromthatofacontrolreactionmixtureintheabsenceofACMSD.Theeffectsofthevariouscompounds(e.g.,TES-1025)ontheenzymeactivityaretestedbyaddingthecompoundstotheassaymixturealongwithACMSD.FortheIC50evaluationsforeachcompound,aserialdilutionfromastocksolutionpreparedinDMSOistested,maintainingaDMSOconcentrationinallthereactionmixturesof1.0%.Oneunitisdefinedastheamountofenzymethatconsume1μmolofACMSperminuteat37°C[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]MaleCD-1miceareused.Thestudyisconductedin3phases.Phase1:18micereceiveanoraladministrationofTES-1025atatargetdoselevelof5mg/kg.Blood,brainandliverarecollectedatintervalsupto8hafterdoseadministration(n=3animalspereachtimepoint).Phase2:3micereceiveeachanintravenousadministrationofTES-1025atatargetdoseof0.5mg/kg.Bloodsamplesarecollectedfromthelateraltailveinatintervalsupto24hafterdoseadministration.Phase3:3micereceiveasingleintravenousadministrationofElacridar(5mg/kg)shortlybeforeanoraladministrationofTES-1025atatargetdoseof5mg/kg.Bloodandbrainsamplesarecollected0.5hafterdoseadministration.Brain,liverandkidneyare2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEcollectedfromallanimalsofthestudy[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產品發表的科研?獻?BiomedPharmacother.2020Dec;132:110836.?ToxicolLett.2021Jun2;S0378-4274(21)00145-4.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].PellicciariR,etal.α-Amino-β-carboxymuconate-ε-semialdehydeDecarboxylase(ACMSD)InhibitorsasNovelModulatorsofDeNovoNicotinamideAdenineDinucleotide(NAD+)Biosynthesis.JMedChem.2018Feb8;61(