Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEIvaltinostatformicCat.No.:HY-16138ASynonyms:CG-200745formic分?式:C??H??N?O?分?量:473.56作?靶點:HDAC;MDM-2/p53;Apoptosis作?通路:CellCycle/DNADamage;Epigenetics;Apoptosis儲存?式:Pureform-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗H2O:50mg/mL(105.58mM;Needultrasonic)DMSO:50mg/mL(105.58mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1117mL10.5583mL21.1166mL5mM0.4223mL2.1117mL4.2233mL10mM0.2112mL1.0558mL2.1117mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(5.28mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.28mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.28mM);ClearsolutionBIOLOGICALACTIVITY?物活性Ivaltinostat(CG-200745)formic?種?服有效的泛HDAC抑制劑，具有異羥肟酸部分，可在催化袋底部結(jié)合鋅。Ivaltinostatformic抑制組蛋?H3和微管蛋?的脫?酰作?。Ivaltinostatformic誘導(dǎo)p53的積累，促進(jìn)p53依賴性反式激活，并增強MDM2和p21(Waf1/Cip1)蛋?的表達(dá)。Ivaltinostatformic可增強Gemcitabine耐藥細(xì)胞對Gemcitabine(HY-16138)和5-Fluorouracil(5-FU;HY-90006)的敏感性。Ivaltinostatformic誘導(dǎo)凋亡并具有抗腫瘤作?。IC50&TargetHDAC體外研究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;for72?hours)inhibitsproliferationofcholangiocarcinomacells(IC50sof0.63,0.93,and1.80?μMforSNU-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?邊的抑制劑?師www.MedChemEWesternBlotAnalysis[4]CellLine:Calu6cellsConcentration:3μMIncubationTime:1,4,8,12,24hoursResult:IncreasedtheacetylationofhistoneH3andH4atvarioussitesinatime-dependentmanner.體內(nèi)研究Ivaltinostat(CG-200745;p.o.;30?mg/kg/day;for7days)formicattenuatesoxidativestress,inflammatorycytokines,andadhesionmoleculesinUUOkidneys[5].AnimalModel:Male8-week-oldC57BL/6?Jmiceweighing20~22?gofunilateralureteralobstruction(UUO)[5]Dosage:30?mg/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