Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEEmodinCat.No.:HY-14393CASNo.:518-82-1分?式:C??H??O?分?量:270.24作?靶點(diǎn):SARS-CoV;CaseinKinase;Autophagy作?通路:Anti-infection;CellCycle/DNADamage;StemCell/Wnt;Autophagy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)Acetone:10.87mg/mL(40.22mM;Needultrasonic)掃描?維碼，DMSO:5.41mg/mL(20.02mM;Needultrasonic)運(yùn)?溶解?案計(jì)算器Ethanol:<1mg/mL(ultrasonic)(insoluble)獲得適合您實(shí)驗(yàn)體系的溶解?案H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.7004mL18.5021mL37.0041mL5mM0.7401mL3.7004mL7.4008mL10mM0.3700mL1.8502mL3.7004mL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，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。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：0.5%MC0.5%Tween-802.Solubility:10mg/mL(37.00mM);Suspendedsolution;Needultrasonic請(qǐng)依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:1.25mg/mL(4.63mM);Suspendedsolution;Needultrasonic1/4www.MedChemEwww.MedChemE此?案可獲得1.25mg/mL(4.63mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。以1mL?作液為例，取100μL12.5mg/mL的澄DMSO儲(chǔ)備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請(qǐng)依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥1.25mg/mL(4.63mM);Clearsolution此?案可獲得≥1.25mg/mL(4.63mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個(gè)?以上的實(shí)驗(yàn)。以1mL?作液為例，取100μL12.5mg/mL的澄DMSO儲(chǔ)備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性Emodin(Frangulaemodin)從植物?屬中分離出來(lái)的?種蒽醌衍?物，?種抗SARS-CoV化合物。Emodin阻斷SARS冠狀病毒刺突蛋?和?管緊張素轉(zhuǎn)化酶2(ACE2)的相互作?[1]。Emodin抑制酪蛋?激酶2(CK2)。具有抗炎和抗癌作?[2]。Emodin還?種有效的選擇性11β-HSD1抑制劑，對(duì)?和??11β-HSD1的IC50分別為186和86nM。Emodin可改飲?誘導(dǎo)的肥胖??的代謝紊亂[3]。IC50&TargetSARS-CoVCK2αWild-typeCK2αWild-typemouse11β-HSD11.4μM(IC50,atATP5.9μM(IC50,atATP86nM(IC50)concentrationis10μconcentrationis50μM)M)human11β-HSD1186nM(IC50)體外研究Emodin(10-400μM)blocksthebindingofSproteintoACE2inadose-dependentmannerwiththeIC50valueof200μM[1].Emodin(5-50μM)inhibitstheSprotein-pseudotypedretrovirusinfectivityinadose-dependentmanner.EmodinblockstheSARS-CoVSproteinbindingtoVeroE6cells[1].Emodininhibitscaseinkinase-2(CK2)withIC50sof5.9,30.0,and7.1μMforCK2αWild-type,Ile174Alamutant,andHis160AlamutantatATPconcentrationis50μM,respectively.TheIC50sare1.40and38.00μMforCK2αWild-type,andVal66AlamutantatATPconcentrationis10μM[2].Emodinexhibitslowinhibitoryactivityagainstmouseandhuman11β-hydroxysteroiddehydrogenasetype2(11β-HSD2),withanIC50higherthan1mM,indicatingthatEmodinismorethan5000-foldselectiveforthehumanandmouse11β-HSD1enzymesoverthetype2isoenzyme[3].CellViabilityAssay[1]CellLine:VeroE6cellstransfectedwiththeplasmidencodingACE2Concentration:0,5,25,50μMIncubationTime:24hoursResult:Verocellstreatedwith50μMremained82.4±3.8%viability,theanti-SARS-CoVactivitywasnotduetotoxicity.2/4www.MedChemEwww.MedChemE體內(nèi)研究Emodin(singleoraladministrationof100or200mg/kg)inhibits11β-HSD1activityinnormalC57BL/6Jmalemice[3].Emodin(100mg/kg;oraladministration;b.i.d.)improvesinsulinsensitivityandlipidmetabolism,andlowersbloodglucoseandhepaticPEPCK,andglucose-6-phosphatasemRNAindiet-inducedobese(DIO)mice[3].AnimalModel:C57BL/6Jmalemice[3]Dosage:100or200mg/kgAdministration:Acuteadministeredp.o.;Twohourslater,themicewerekilledbycervicaldislocation,Result:Significantlyinhibitedliver11β-HSD1enzymaticactivityby17.6and31.3%andmesentericfat11β-HSD1enzymaticactivityby21.5and46.7%at100or200mg/kg,respectively.AnimalModel:DIOmice(C57BL/6Jmalemicewerefedaformulatedresearchdiet)[3]Dosage:100mg/kgAdministration:Oralgavage;twiceperday;for35daysResult:Reducedfastingglucoseconcentrationsto77.2%ofthevehiclecontrolmiceafter7daysoftreatment,andtheseremainedsignificantlylowerthroughoutthetreatmentperiod.Exhibitedasignificantreductioninbloodglucoselevelsatalltime-pointsfollowingoralglucosechallengeafter24daysoftreatment.Evokedasignificantlygreaterreductioninbloodglucosevalues40and90minafterinsulininjectionafter28daysoftreatment.Theseruminsulinlevelwasalsosignificantlyreduced,to66.2%ofcontrolmice,after35daysoftreatment.Improvedthelipidprofiles.Theserumtriglycerideandtotalcholesterollevelsweresignificantlyreducedby19.3and12.5%after35daysoftreatment,respectively.Causeda22.7%reductionofnon-esterifiedfreefattyacid(NEFA)level.Loweredbodyweightandappetitefromday18ofthetreatment;theirbodyweightswerereducedby13.9%attheendoftreatment.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NucleicAcidsRes.2021Jan8;49(D1):D1113-D1121.?ActaPharmacolSin.2021Jan;42(1):108-114.?IntImmunopharmacol.2020Dec23;91:107277.?IntImmunopharmacol.2020Nov;88:107020.?ExpCellRes.2020Aug1;393(1):112054.Seemorecustomervalidationsonwww.MedChemE3/4www.MedChemEwww.MedChemEREFERENCES[1].Tin-YunHo,etal.EmodinblockstheSARScoronavirusspikeproteinandangiotensin-convertingenzyme2interaction.AntiviralRes.2007May;74(2):92-101.[2].YingFeng,etal.Emodin,anaturalproduct,selectivelyinhibits11beta-hydroxysteroiddehydrogenasetype1andamelioratesmetabolicdisorderindiet-inducedobesemice.BrJPharmacol.2010Sep;161(1):113-26.[3].StefaniaSarno,etal.Towardtherationaldesignofproteinkinasecaseinkinase-2inhibitors.PharmacolTher.Feb-Mar2002;93(2