Toyocamycin-Vengicide-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEToyocamycinCat.No.:HY-103248CASNo.:606-58-6Synonyms:Vengicide分⼦式:C₁₂H₁₃N₅O₄分⼦量:291.26作⽤靶点:IRE1;Fungal;Antibiotic;Apoptosis;CDK作⽤通路:CellCycle/DNADamage;Anti-infection;Apoptosis储存⽅式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(343.34mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.4334mL17.1668mL34.3336mL5mM0.6867mL3.4334mL6.8667mL10mM0.3433mL1.7167mL3.4334mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(8.58mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.58mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.58mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Toyocamycin(Vengicide)链霉类产⽣的腺苷类似物，X盒结合蛋⽩1(XBP1)抑制剂。Toyocamycin可阻断RNA合成和核糖体功能，并诱导凋亡(apoptosis)。Toyocamycin响IRE1α-XBP1通路，抑制XBP1mRNA断裂(IC50=80nM)，不响IRE1α⾃⾝磷酸化。Toyocamycin特异性抑制CDK9，IC50为79nM。IC50&TargetCDK9/cyclinT1CDK7/Mat1/cyclinH1CDK2/cyclinACdk4/cyclinD379nM(IC50)2.8μM(IC50)0.67μM(IC50)15μM(IC50)cdk6/cyclinD3>10μM(IC50)体外研究Toyocamycin(0-0.3μM;4h)inhibitsERstress-inducedXBP1mRNAsplicing,andselectivelyinhibitstheERstress-inducedactivationoftheIRE1α-XBP1pathway[1].Toyocamycin(0-0.3μM;24h)inhibitsconstitutiveactivationofXBP1inMMcelllines[1].Toyocamycin(250nM;48h)inhibitsCDK9enzymaticactivityincoloncancercelllines[2].Toyocamycin(0.05nM-50μM;48hand72h)doesn’ttriggerimmediatecytotoxicityagainstYB5andHCT116cellswithcellviabilityabove50%,butresultseradicationofcancercells2weekslaterat10nMfor24htreatment[2].Toyocamycin(0-100nM;24or48h)inducesapoptosisviamitochondrialpathwayinPC-3cells[3].Toyocamycin(60nM;0-48h)promotesp38/ERKMAPKactivationandregulatesROS-mediatedapoptosisbyinhibitionofp38onERKMAPK[3].WesternBlotAnalysis[1]CellLine:HeLa,HEK293Concentration:0,0.03,0.1,0.3μMIncubationTime:4hoursResult:Suppressedneithertunicamycin-inducedATF6norPERKactivation.InhibitedIRE1α-inducedXBP1mRNAcleavagewithoutaffectingIRE1αphosphorylationonSer724.WesternBlotAnalysis[3]CellLine:HumanprostatecancerPC-3cellsConcentration:60nM2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:12,24,36,48hoursResult:SuppressedthephosphorylationlevelofAKA,whiledecreasingthephosphorylationlevelofERKandp38.CellViabilityAssay[3]CellLine:PC-3andRWPE-1cellsConcentration:0,20,40,60,80,100nMIncubationTime:24or48hoursResult:Inhibtedcellviabilityandinducedcellapoptosisby62%.体内研究Toyocamycin(0.5mg/kg,1.0mg/kg;i.p.;twiceaweek;2weeks)showsanti-tumoractivityinaxenograftmodelwithhumanmultiplemyeloma(MM)cells,whiletheanti-tumoreffectenhancedbyBortezomib(HY-10227)[1].AnimalModel:SCIDmiceinjectedwithhumanmultiplemyeloma(MM)cells[1]Dosage:0.5mg/kg,1.0mg/kgAdministration:Intraperitonealinjection;twiceaweek;2weeksResult:Reducedthetumorvolumesignificantly.Showedenhancinganti-tumoractivityrepresentedassmallertumorvolumeswhencomparedwithBortezomib(HY-10227).REFERENCES[1].PandeyS,etal.SelectiveCDK9InhibitionbyNaturalCompoundToyocamycininCancerCells.Cancers(Basel).2022Jul8;14(14):3340.[2].ParkSG,etal.Toyocamycininducesapoptosisviathecrosstalkbetweenreactiveoxygenspeciesandp38/ERKMAPKssignalingpathwayinhumanprostatecancerPC-3cells.PharmacolRep.2017Feb;69(1):90-96.[3].Toyocamycin,etal.IdentificationofToyocamycin,anagentcytotoxicformultiplemyelomacells,asapotentinhibitorofERstress-inducedXBP1mRNAsplicing.BloodCancerJ.2012Jul;2(7):