Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGSK621Cat.No.:HY-100548CASNo.:1346607-05-3分?式:C??H??ClN?O?分?量:489.91作?靶點(diǎn):AMPK;Autophagy;Apoptosis作?通路:Epigenetics;PI3K/Akt/mTOR;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:12.5mg/mL(25.51mM;ultrasonicandadjustpHto1withHCl)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.0412mL10.2060mL20.4119mL5mM0.4082mL2.0412mL4.0824mL10mM0.2041mL1.0206mL2.0412mL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%salineSolubility:1.25mg/mL(2.55mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—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:≥1.25mg/mL(2.55mM);Suspendedsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.25mg/mL(2.55mM);Clearsolution4.請(qǐng)依序添加每種溶劑：50%PEG300>>50%salineSolubility:10mg/mL(20.41mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性GSK621特異性的AMPK激動(dòng)劑，其對(duì)AML細(xì)胞系的IC50值為13-30μM。GSK621可誘導(dǎo)?噬和凋亡。GSK621可誘導(dǎo)eiF2α磷酸化(UPR激活的?個(gè)標(biāo)志)。體外研究GSK621(30μM)inducesAMPKαT172,ACC(S79)andULK1(S555)phosphorylation[1].GSK621(30μM)inducesautophagyandapoptosis[1].GSK621treatmentalsoinducesPERKphosphorylation,amarkerofERstress,inAMLcells[1].CellProliferationAssay[1]CellLine:MV4-11,OCI-AML3,OCI-AML2,HL-60,Kasumi,HEL,UT7,NB4,TF-1,KG1A,Nomop28,SKM-1,U937,YHP1,MOLM-14,Mo7e,K562,MOLM-13,EOL-1,SET-2AMLcelllines.0-30μM.Concentration:0-30μM.IncubationTime:4d.Result:IC50valuesrangedfrom13to30μM.Reducedtheproliferationofall20linesandincreasedapoptosisin17(85%)lines.CellAutophagyAssay[1].CellLine:AMLcelllinesandprimaryAMLsamples.Concentration:30μM.IncubationTime:24h.Result:Inducedtheformationofnumerousintracytoplasmicvacuolesincludingautophagosomes.體內(nèi)研究GSK621(30mg/kg,iptwicedaily)exhibitssignificantanti-tumoractivityinMOLM-14cellsxenograft[1].AnimalModel:MOLM-14cellsxenograftedintonudemice[1].Dosage:30mg/kg.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration:IPtwicedaily.Result:Reducedleukemiagrowthandsignificantlyextendedsurvivalcomparedtovehicle-treatedanimalsorthosetreatedwith10mg/kgtwicedaily.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?EMBOJ.2021Sep2;e108028.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].PierreSujobert,etal.Co-activationofAMPKandmTORC1InducesCytotoxicityinAcuteMyeloidLeukemia.CellRep.2015Jun9;11(9):1446-57.McePdfHeightCaution:Producthasnotbeenfullyvalidatedfor