Colchicine-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEColchicineCat.No.:HY-16569CASNo.:64-86-8分?式:C??H??NO?分?量:399.44作?靶點(diǎn):Microtubule/Tubulin;Autophagy;Apoptosis作?通路:CellCycle/DNADamage;Cytoskeleton;Autophagy;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥48mg/mL(120.17mM)H2O:≥33.33mg/mL(83.44mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.5035mL12.5175mL25.0350mL5mM0.5007mL2.5035mL5.0070mL10mM0.2504mL1.2518mL2.5035mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：PBSSolubility:2.78mg/mL(6.96mM);Clearsolution;Needultrasonicandwarmingandheatto60°CBIOLOGICALACTIVITY?物活性Colchicine微管蛋?(tubulin)抑制劑和微管(microtubule)?擾劑。Colchicine抑制微管聚合的IC50為3nM[1][2][3]。Colchicine還α3?氨酸受體(GlyRs)的競爭性拮抗劑[4]。IC50&TargetMicrotubule/Tubulin[1]體外研究Exposureto1μMColchicine,amicrotubuledisruptingagent,triggeredapoptosisinratcerebellargranulecells(CGC).ColchicinetreatmentalsocausesalterationsinCa2+responsestochemicaldepolarizationandamoderate,butprogressive,increaseintherestingintracellularCa2+concentration[1].Colchicineexertsitsbiologicaleffectsthroughbindingtothesolubletubulinheterodimer,themajorcomponentofthemicrotubule.TheColchicinebindingabilitiesoftubulinsfromavarietyofsourcesaresummarized,andthemechanismofColchicinebindingtobraintubulinisexploredindepth.TherelationshipbetweencolchicinoidstructureandtubulinbindingactivityprovidesinsightintothestructuralfeaturesofColchicineresponsibleforhighaffinitybindingtotubulinandisreviewedforanalogsintheColchicineseries.Thethermodynamicandkineticaspectsoftheassociationaredescribedandevaluatedintermsofthebindingmechanism.ColchicinebindingtotubulinresultsinunusualalterationsinthelowenergyelectronicspectraofColchicine.ThespectroscopicfeaturesofColchicineboundtotubulinarediscussedintermsofthenatureoftheColchicine-tubulincomplex.AttemptstolocatethehighaffinityColchicinebindingsiteontubulinarepresented[2].Colchicinetreatmentinhibitsindomethacin-inducedsmallintestinalinjuryby86%(1mg/kg)and94%(3mg/kg)asindicatedbythelesionindex24hafterindomethacinadministration.Colchicineinhibitstheproteinexpressionofcleavedcaspase-1andmatureIL-1β,withoutaffectingthemRNAexpressionofNLRP3andIL-1β[3].體內(nèi)研究VehicleorColchicine(1mg/kg)isadministeredorally30minpriortoindomethacinadministration.ThelesionsstainedwithEvansblueinthesmallintestinearesmallerinColchicine-treatedmicethanthoseinvehicle-treatedmice24hafterindomethacinadministration.Inaddition,histologicalexaminationshowsthatColchicine-treatedmicehavelessmucosalinflammationandulcerationandadecreaseinthesizeandnumbersoflesionscomparedwithvehicle-treatedmice.Colchicinetreatmentsignificantlyreducesthelesionindexatdosesof1mg/kgand3mg/kg(by86%and94%,respectively)comparedwithvehicletreatment.ColchicinetreatmentsignificantlyinhibitstheproteinlevelsofmatureIL-1βatdosesof1mg/kgand3mg/kg(by56%and69%,respectively)withoutaffectingthoseofpro-IL-1β.Colchicinetreatmentalsosignificantlyinhibitstheproteinlevelsofcleavedcaspase-1atdosesof1mg/kgand3mg/kg(by26%and39%,respectively)withoutaffectingthoseofpro-caspase-1[3].PROTOCOLAnimalMice[3]Administration[3]Specific-pathogen-free8-week-oldmalemiceareused.Wild-typeC57BL/6miceandNLRP3?/?miceona2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEC57BL/6backgroundareused.ToexaminetheeffectsofColchicineonNSAID-inducedsmallintestinalinjury,vehicleorColchicine(1or3mg/kg)isadministeredorally30minpriortoindomethacinadministration.MicereceivedintraperitonealinjectionsofsterilizedphosphatebufferedsalineormouserecombinantIL-1β(0.1μg/kg)3hafterindomethacintreatment.VehicleorColchicine(1or3mg/kg)isalsoadministeredtoNLRP3?/?micebeforeindomethacinadministration.Thelesionindexisevaluated24hafterindomethacinadministration,andexaminedmRNAandproteinexpressionofinflammasomecomponents6hafterindomethacinadministration.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatCommun.2020Sep29;11(1):4902.?ActaPharmSinB.2022Sep;12(9):3618-3638.?EMBOJ.2020Jul1;39(13):e104168.?StemCellResTher.2022Sep2;13(1):436.?MolOncol.2022Mar;16(6):1347-1364.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BonfocoE,etal.Colchicineinducesapoptosisincerebellargranulecells.ExpCellRes.1995May;218(1):189-200.[2].HastieSB.Interactionsofcolchicinewithtubulin.PharmacolTher.1991;51(3):377-401[3].OtaniK,etal.ColchicinepreventsNSAID-inducedsmallintestinalinjurybyinhibitingactivationoftheNLRP3inflammasome.SciRep.2016Sep2;6:32587.[4].CarolaMu?oz-Montesino,etal.InhibitionoftheGlycineRecep