Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGLPG0187Cat.No.:HY-100506CASNo.:1320346-97-1分?式:C??H??N?O?S分?量:595.71作?靶點(diǎn):Integrin作?通路:Cytoskeleton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:12.5mg/mL(20.98mM;ultrasonicandwarmingandheatto60°C)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.6787mL8.3933mL16.7867mL5mM0.3357mL1.6787mL3.3573mL10mM0.1679mL0.8393mL1.6787mL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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥1.25mg/mL(2.10mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.25mg/mL(2.10mM);Clearsolution3.請(qǐng)依序添加每種溶劑：20%HP-β-CDinsalineSolubility:10mg/mL(16.79mM);Suspensionsolution;Needultrasonic4.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥0.89mg/mL(1.49mM);Clearsolution5.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥0.89mg/mL(1.49mM);ClearsolutionBIOLOGICALACTIVITY?物活性GLPG0187?譜的integrin受體拮抗劑，具有抗腫瘤活性；抑制αvβ1-integrin的IC50值為1.3nM。GLPG0187抑制細(xì)胞遷移體?物合成??細(xì)胞毒性。IC50&TargetIC50:1.3nM(αvβ1)[1]體外研究Inasolid-phaseassay,GLPG0187showsselectivityforseveralRGDintegrinreceptorswithIC50sof1.3,3.7,2.0,1.4,1.2,7.7nMforαvβ1,αvβ3,αvβ5,αvβ6,αvβ8,andα5β1.GLPG0187isapotentinhibitorofosteoclasticboneresorptionandangiogenesis.TreatmentwithGLPG0187dose-dependentlyincreasestheE-cadherin/vimentinratio,renderingthecellsamoreepithelial,sessilephenotype.GLPG0187dose-dependentlydiminishesthesizeofthealdehydedehydrogenasehighsubpopulationofprostatecancercells[1].GLPG0187treatmentresultsincellroundingandclumping.GLPG0187demonstratesadose-dependentsignificantreductionintumourcellmigration.GLPG0187atallconcentrationssignificantlyreducescellproliferation[2].體內(nèi)研究Blockingαv-integrinsbyGLPG0187markedlyreducestheirmetastatictumorgrowth.Bonetumorburdenissignificantlylowerandthenumberofbonemetastases/mouseissignificantlyinhibited.Theprogressionofbonemetastasesandtheformationofnewbonemetastasesduringthetreatmentperiodissignificantlyinhibited[1].PROTOCOLCellAssay[2]TumourcellproliferationisdeterminedusingtheMTSassay.PC3cellsareseededat10,000cells/wellin96wellplatescontainingeitherGLPG0187(0.5,5,or50ng/mL),vehicleormediacontrol,thenculturedin100μLmediumfor24hr.Cellproliferationisanalysedusing20μLMTSdyeincubatedfor3hrat37°Cinthedark.Absorbancefromeachwell(6/treatment)isquantifiedat490nmandthemeanfluorescencecalculated.Theassayisrepeatedat48,72and96hr,onthreeindependentoccasions[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:TheeffectofGLPG0187onbonelossisevaluatedin3-month-oldcastratedmalemiceafter4weeksofAdministration[1]treatmentwithdosingstartingimmediatelyaftercastration(preventiveprotocol).Twodifferentmodesof2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEadministrationareused:eithersubcutaneoustwicedailywith10,30,or100mg/kgofGLPG0187,eitheroral,twicedailywith30,100,or300mg/kgofGLPG0187[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Cell.2021Sep16;184(19):4919-4938.e22.?Gut.2021Jan19;gutjnl-2020-323719.?OxidMedCellLongev.2020May16;2020:6384803.?JPharmaceutBiomed.2021Feb20;195:113825.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].PuzhongLu,etal.ChemicalscreeningidentifiesROCK1asaregulatorofmigrasomeformation.CellDiscov.2020Aug4;6(1):51.[2].vanderHorstG,etal.Targetingofα(v)-integrinsinstem/progenitorcellsandsupportivemicroenvironmentimpairsbonemetastasisinhumanprostatecancer.Neoplasia.2011Jun;13(6):516-25.[3].ReevesKJ,etal.Prostatecancercellshometoboneusinganovelinvivomodel:modulationbytheintegrinantagonistGLPG0187.IntJCancer.2015