Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemES130Cat.No.:HY-112818CASNo.:1160852-22-1分?式:C??H??N?O?分?量:387.47作?靶點(diǎn):Cathepsin;Autophagy;Apoptosis作?通路:MetabolicEnzyme/Protease;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:125mg/mL(322.61mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.5808mL12.9042mL25.8084mL5mM0.5162mL2.5808mL5.1617mL10mM0.2581mL1.2904mL2.5808mL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.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.25mg/mL(5.81mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.25mg/mL(5.81mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.37mM);ClearsolutionBIOLOGICALACTIVITY?物活性S130?種?親和?、選擇性的半胱氨酸蛋?酶ATG4B的抑制劑,IC50值為3.24μM。S130可以抑制?噬通量[1]。IC50&TargetIC50:3.24μM(ATG4B)[1]體外研究S130suppressesautophagyandactivatesapoptosisbyinhibitingATG4B,leadstoenhancedcytotoxicity[1].S130(10μM;6hours)suppressesautophagyattheearlyLC3primingsteporlateautolysosomedegradationstage[1].S130accumulatesautolysosomeswithmorelipidatedLC3[1].S130(0-25μM;48hours)inducescelldeaththroughinhibitingtheactivityofATG4Batadosehigherthan6.3μM.Andsuchcytotoxicitymightnotcausecelldeaththroughnecroptosis[1].NutrientdeprivationenhancesS130-inducedcytotoxicity[1].S130(0-10μM;24hours)suppressesapproximately79%ofthecleavageoffull-lengthLC3-GSTatthe10μM,whilenosubstrateswereprocessedinATG4BKOcells.S130displaysobviousinhibitoryeffectsonATG4B[1].CellCytotoxicityAssay[1]CellLine:HeLacells,HCT116cells,HL60cellsConcentration:0μM,3.1μM,6.3μM,12.5μM,25μMIncubationTime:48hoursResult:HadsignificantcytotoxiceffectsonHeLacells(IC50=16.1μM),HCT116cells(IC50=9.0μM)andHL60cells(IC50=4.7μM)atadosehigherthan6.3μM.Andsuchcytotoxicitymightnotcausecelldeaththroughnecroptosis.CellAutophagyAssay[1]CellLine:HeLacellsandMEFcellsConcentration:10μMIncubationTime:6hoursResult:SuppressedautophagyattheearlyLC3primingsteporlateautolysosomedegradationstage.WesternBlotAnalysis[1]2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:HeLacellsConcentration:0μM,5μM,10μMIncubationTime:24hoursResult:Suppressedapproximately79%ofthecleavageoffull-lengthLC3-GSTat10μM,whilenosubstrateswereprocessedinATG4BKOcells.體內(nèi)研究S130(20mg/kg;i.p.;daily;3weeks)suppressestumorgrowth,andshowsanefficientinvivoantitumoreffectwithasoundsafetyonvitalorgans[1].AnimalModel:BALB/cnudefemalemice(4weeks),withHCT116cellsxenograft[1]Dosage:20mg/kgAdministration:Intraperitonealinjection;daily;3weeksResult:Wasabletosuppresstumorgrowthandwithasoundsafetyonvitalorgans.REFERENCES[1].FuY,etal.DiscoveryofasmallmoleculetargetingautophagyviaATG4Binhibitionandcelldeathofcolorectalcancercellsinvitroandinvivo.Autophagy.2018Sep20:1-17.McePdfHeightCaution:Producthas