Ivaltinostat-formic-CG-200745-formic-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEIvaltinostatformicCat.No.:HY-16138ASynonyms:CG-200745formic分⼦式:C₂₅H₃₅N₃O₆分⼦量:473.56作⽤靶点:HDAC;MDM-2/p53;Apoptosis作⽤通路:CellCycle/DNADamage;Epigenetics;Apoptosis储存⽅式:Pureform-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验H2O:50mg/mL(105.58mM;Needultrasonic)DMSO:50mg/mL(105.58mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1117mL10.5583mL21.1166mL5mM0.4223mL2.1117mL4.2233mL10mM0.2112mL1.0558mL2.1117mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.28mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.28mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.28mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Ivaltinostat(CG-200745)formic⼀种⼝服有效的泛HDAC抑制剂，具有异羟肟酸部分，可在催化袋底部结合锌。Ivaltinostatformic抑制组蛋⽩H3和微管蛋⽩的脱⼄酰作⽤。Ivaltinostatformic诱导p53的积累，促进p53依赖性反式激活，并增强MDM2和p21(Waf1/Cip1)蛋⽩的表达。Ivaltinostatformic可增强Gemcitabine耐药细胞对Gemcitabine(HY-16138)和5-Fluorouracil(5-FU;HY-90006)的敏感性。Ivaltinostatformic诱导凋亡并具有抗肿瘤作⽤。IC50&TargetHDAC体外研究Ivaltinostat(CG-200745;0.01-100μM;48hours)formicinhibitsgrowthofprostatecancercells(LNCaP,DU145andPC3cells).Ivaltinostat(1,10μM;24,48hours)formicincreasessub-G1population,andactivatescaspase-9,-3and-8[2].Ivaltinostat(0.001-100μM;for72ꢀhours)inhibitsproliferationofcholangiocarcinomacells(IC50sof0.63,0.93,and1.80ꢀμMforSNU-1196,SNU-1196/GR,SNU-308cells,respectively)[3].Ivaltinostat(0-10μM;48hours)formicreducestheCalu6cellsproliferationto40%ofuntreatedcells[4].Ivaltinostat(3μM;1-24hours)formicsignificantlyincreasesCalu6cellsproportioninG2/Mphase(69%)[4].Ivaltinostat(0-10μM;1-24hours)formictreatmentwithlowconcentrationsignificantlyincreasestheacetylationofhistoneH3andH4inCalu6cellsatvarioussitesinatime-dependentmannerupto24hoursaftertreatment[4].CellProliferationAssay[4]CellLine:Calu6cellsConcentration:0-10μMIncubationTime:48hoursResult:Reducedthecellproliferationto40%ofuntreatedcells.CellCycleAnalysis[4]CellLine:Calu6cellsConcentration:3μMIncubationTime:1,8,12,24hoursResult:IncreasedsignificantlycellproportioninG2/Mphase(69%).2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEWesternBlotAnalysis[4]CellLine:Calu6cellsConcentration:3μMIncubationTime:1,4,8,12,24hoursResult:IncreasedtheacetylationofhistoneH3andH4atvarioussitesinatime-dependentmanner.体内研究Ivaltinostat(CG-200745;p.o.;30ꢀmg/kg/day;for7days)formicattenuatesoxidativestress,inflammatorycytokines,andadhesionmoleculesinUUOkidneys[5].AnimalModel:Male8-week-oldC57BL/6ꢀJmiceweighing20~22ꢀgofunilateralureteralobstruction(UUO)[5]Dosage:30ꢀmg/kgAdministration:PO;daily;for7daysResult:Attenuatedoxidativestress,inflammatorycytokinesandadhesionmoleculesinUUOkidneys.REFERENCES[1].OhET,etal.NovelhistonedeacetylaseinhibitorCG200745inducesclonogeniccelldeathbymodulatingacetylationofp53incancercells.InvestNewDrugs.2012Apr;30(2):435-42.[2].HwangJJ,etal.Anovelhistonedeacetylaseinhibitor,CG200745,potentiatesanticancereffectofdocetaxelinprostatecancerviadecreasingMcl-1andBcl-XL.InvestNewDrugs.2012Aug;30(4):1434-42.[3].ChunSM,etal.EpigeneticmodulationwithHDACinhibitorCG200745inducesanti-proliferationinnon-smallcelllungcancercells.PLoSOne.2015Mar17;10(3):e0119379.[4].ChoiHS,etal.Histonedeacetylaseinhibitor,CG200745attenuatesrenalfibrosisinobstructivekidneydisease.SciRep.2018Aug1;8(1):11546.[5].DawoonEJung,etal.CG200745,anHDACinhibitor,inducesanti-tumoureffectsincholangiocarcinomacelllinesviamiRNAstargetingtheHippopathway.SciRep.2017Sep7;7