Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGSTO1-IN-1Cat.No.:HY-111530CASNo.:568544-03-6分?式:C??H??Cl?N?O?S分?量:311.18作?靶點(diǎn):GutathioneS-transferase作?通路:MetabolicEnzyme/Protease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:≥300mg/mL(964.07mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.2136mL16.0679mL32.1357mL5mM0.6427mL3.2136mL6.4271mL10mM0.3214mL1.6068mL3.2136mL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:≥2.5mg/mL(8.03mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.03mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.03mM);ClearsolutionBIOLOGICALACTIVITY?物活性GSTO1-IN-1?種有效的?胱?肽S-轉(zhuǎn)移酶omega1(GSTO1)抑制劑，IC50為31nM。IC50&TargetIC50:31nM(GSTO1)[1]體外研究GSTO1-IN-1(C1-27)potentlyinhibitsGSTO1enzymeactivitywithanIC50valueof31nM.GSTO1-IN-1alsopotentlycompeteswith5-chloromethylfluoresceindiacetate(CMFDA)forbindingtorecombinantprotein,aswellasendogenousGSTO1inthemilieuofasolubleproteome.HCT116cellstreatedwithGSTO1-IN-1alsoshowadecreaseincellviabilityinadose-dependentmanner.GSTO1-IN-1inhibitstheclonogenicsurvivalofHCT116cellsatsub-micromolarconcentrations[1].體內(nèi)研究TotestwhetherGSTO1-IN-1hadinvivoefficacy,itseffectsareevaluatedinahumancoloncancercelllinexenograftmodel.GSTO1-IN-1(20-45mg/kg)isadministeredasasingleagenttonudemicebearingHCT116xenografts.After5weeksoftreatment,tumorgrowthissignificantlyinhibitedinGSTO1-IN-1-treatedmicecomparedwiththevehicle-treatedgroup(P[1].PROTOCOLCellAssay[1]CellproliferationisassessedbyaMTTassay.CancercellsH630,HT29andHCT116areseededin96-wellmicrotitreplatesand,afterovernightattachment,treatedwithGSTO1inhibitors(e.g.,GSTO1-IN-1;0.1,1,10and100μM).After72h,MTTsolution(3mg/mL;20mL)isaddedtoeachwellandcellsareincubatedfor3hat37°C.Afterincubation,mediafromeachwellisremovedandthedarkblueformazancrystalsformedbylivecellsaredissolvedinDMSO(150mLperwell).Theabsorbanceintensityismeasuredat570nmonamicroplatereader.Cellviabilityafter24htreatmentisassessedusingApoTox-Glotriplexassay.Atleastthreeindependentdose-responseexperimentswitheachconcentrationtestedintriplicateareperformedforeachcellline[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]Inthepilotstudy,HCT116cells(1×106)inexponentialphaseareinjectedsubcutaneouslyintotheleftflankof8-to10-week-oldfemalenudemice(25-30g).Theperpendiculardiametersofthetumorsaremeasuredthreetimesweeklyusingstandardcalipersandtumourvolumesarecalculated.Tumorsareallowedtogrowtoavolumeof50mm3andmicearerandomizedintocontrol(n=5)andGSTO1-IN-1(n=3)treatmentgroups.GSTO1-IN-1isadministeredintraperitoneally(20mg/kgperday)forthefirst2weeksona5dayson/2daysoffschedule.Thedoseisthenincreasedto25mg/kgperdayforthenext23daysandfurtherescalatedby52/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEmg/kgperdaytoafinaldoseof45mg/kgfortheremainingdurationoftreatment.Tumorvolumesandbodyweightsaremeasuredthreetimesweeklytomonitortumorburdenandweightlossduringtreatment.Attheendoftheexperiment,animalsarekilledandtumor,kidneyandliverarecollected,fixedandparaffinembeddedforhistology[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?bioRxiv.June28,2021.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RamkumarK,etal.MechanisticevaluationandtranscriptionalsignatureofaglutathioneS-transferaseomega1inhibitor.NatCommun.2016