TES-1025-DataSheet-生命科学试剂-MedChemExpressVIP

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETES-1025Cat.No.:HY-111365CASNo.:1883602-21-8分⼦式:C₁₈H₁₃N₃O₃S₂分⼦量:383.44作⽤靶点:Others作⽤通路:Others储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(260.80mM;Needwarming)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.6080mL13.0399mL26.0797mL5mM0.5216mL2.6080mL5.2159mL10mM0.2608mL1.3040mL2.6080mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.52mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.52mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性TES-1025⼀种有效的和选择性⼈α-氨-β-羧粘康酸-ε-半醛脱羧酶(ACMSD)抑制剂，IC50为13nM[1]。IC50&TargetIC50:13±3nM(humanACMSD)[1]体外研究TES-1025isalownanomolarhumanACMSDinhibitor,whichincreasesNAD+levelsincellularsystems[1].体内研究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-1025isfurtherconfirmedintheliverandkidneyswithAUC0-8hof19ꢀ200h•ng/mLand36ꢀ600h•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—您⾝边的抑制剂⼤师www.MedChemEcollectedfromallanimalsofthestudy[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•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(