MedKoo Biosciences/Romidepsin/100764/25mg

Synonym:FK228;FK-228;FK228;FR901228;FR-901228;FR901228;NSC630176.depsipeptide;USbrandname:Istodax.

IUPAC/ChemicalName:(1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-bis(1methylethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazABIcyclo[8.7.6]tricos-16ene-3,6,9,19,22-pentone

InChiKey:OHRURASPPZQGQM-GCCNXGTGSA-N

InChiCode:InChI=1S/C24H36N4O6S2/c1-6-16-21(30)28-20(14(4)5)24(33)34-15-9-7-8-10-35-36-12-17(22(31)25-16)26-23(32)19(13(2)3)27-18(29)11-15/h6-7,9,13-15,17,19-20H,8,10-12H2,1-5H3,(H,25,31)(H,26,32)(H,27,29)(H,28,30)/b9-7+,16-6-/t15-,17-,19-,20+/m1/s1

SMILESCode:O=C([C@H](C(C)C)NC(/C(N1)=C/C)=O)O[C@](CC(N[C@H](C(C)C)C(N2)=O)=O)([H])/C=C/CCSSC[C@]2([H])C1=O

TechnicalData

AdditionalInformation

Romidepsin,ahistonedeacetylase(HDAC)inhibitor,isabicyclicdepsipeptide.Atroomtemperature,romidepsinisawhitepowderandisdescribedchemicallyas(1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-bis(1methylethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricos-16ene-3,6,9,19,22-pentone.TheempiricalformulaisC24H36N4O6S2.ISTODAX(romidepsin)forinjectionisintendedforintravenousinfusiononlyafterreconstitutionwiththesuppliedDiluentandafterfurtherdilutionwith0.9%SodiumChloride,USP.ISTODAXissuppliedasakitcontainingtwovials.ISTODAX(romidepsin)forinjectionisasterilelyophilizedwhitepowderandissuppliedinasingle-usevialcontaining10mgromidepsinand20mgpovidone,USP.DiluentforISTODAXisasterileclearsolutionandissuppliedinasingle-usevialcontaininga2-mLdeliverablevolume.DiluentforISTODAXcontains80%(v/v)propyleneglycol,USPand20%(v/v)dehydratedalcohol,USP.
  
Accordingtohttp://en.wikipedia.org/wiki/Romidepsin,Romidepsinwasfirstreportedinthescientificliteraturein1994,byateamofresearchersfromFujisawaPharmaceuticalCompany(nowAstellasPharma)inTsukuba,Japan,whoisolateditinacultureofChromobacteriumviolaceumfromasoilsampleobtainedinYamagataPrefecture.Itwasfoundtohavelittletonoantibacterialactivity,butwaspotentlycytotoxicagainstseveralhumancancercelllines,withnoeffectonnormalcells;studiesonmicelaterfoundittohaveantitumoractivityinvivoaswell.ThefirsttotalsynthesisofromidepsinwasaccomplishedbyHarvardresearchersandpublishedin1996.Itsmechanismofactionwaselucidatedin1998,whenresearchersfromFujisawaandtheUniversityofTokyofoundittobeahistonedeacetylaseinhibitorwitheffectssimilartothoseoftrichostatinA.RomidepsinisbrandedandownedbyGloucesterPharmaceuticals,nowapartofCelgene.OnNovember5,2009,itwasapprovedbytheU.S.FoodandDrugAdmiNISTrationforthetreatmentofCTCL,afterfiveyearsintheagency'sfasttrackdevelopmentprogram.
  
MechanismofAction
Romidepsinisahistonedeacetylase(HDAC)inhibitor.HDACscatalyzetheremovalofacetylgroupsfromacetylatedlysineresiduesinhistones,resultinginthemodulationofgeneexpression.HDACsalsodeacetylatenon-histoneproteins,suchastranscriptionfactors.Invitro,romidepsincausestheaccumulationofacetylatedhistones,andinducescellcyclearrestandapoptosisofsomecancercelllineswithIC50valuesinthenanomolarrange.Themechanismoftheantineoplasticeffectofromidepsinobservedinnonclinicalandclinicalstudieshasnotbeenfullycharacterized.
 

References

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