Toyocamycin-Vengicide-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEToyocamycinCat.No.:HY-103248CASNo.:606-58-6Synonyms:Vengicide分?式:C??H??N?O?分?量:291.26作?靶點(diǎn):IRE1;Fungal;Antibiotic;Apoptosis;CDK作?通路:CellCycle/DNADamage;Anti-infection;Apoptosis儲(chǔ)存?式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(343.34mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.4334mL17.1668mL34.3336mL5mM0.6867mL3.4334mL6.8667mL10mM0.3433mL1.7167mL3.4334mL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:≥2.5mg/mL(8.58mM);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:≥2.5mg/mL(8.58mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.58mM);ClearsolutionBIOLOGICALACTIVITY?物活性Toyocamycin(Vengicide)鏈霉類(lèi)產(chǎn)?的腺苷類(lèi)似物，X盒結(jié)合蛋?1(XBP1)抑制劑。Toyocamycin可阻斷RNA合成和核糖體功能，并誘導(dǎo)凋亡(apoptosis)。Toyocamycin響IRE1α-XBP1通路，抑制XBP1mRNA斷裂(IC50=80nM)，不響IRE1α??磷酸化。Toyocamycin特異性抑制CDK9，IC50為79nM。IC50&TargetCDK9/cyclinT1CDK7/Mat1/cyclinH1CDK2/cyclinACdk4/cyclinD379nM(IC50)2.8μM(IC50)0.67μM(IC50)15μM(IC50)cdk6/cyclinD3>10μM(IC50)體外研究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?邊的抑制劑?師www.MedChemEIncubationTime:12,24,36,48hoursResult:SuppressedthephosphorylationlevelofAKA,whiledecreasingthephosphorylationlevelofERKandp38.CellViabilityAssay[3]CellLine:PC-3andRWPE-1cellsConcentration:0,20,40,60,80,100nMIncubationTime:24or48hoursResult:Inhibtedcellviabilityandinducedcellapoptosisby62%.體內(nèi)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):