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{{short description|Chemical compound}} |
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{{Drugbox |
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{{Drugbox |
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| IUPAC_name = (1''S'',4''S'',7''Z'',10''S'',16''E'',21''R'')-7-ethylidene-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetrazabicyclotricos-16-ene-3,6,9,19,22-pentone |
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| image = Romidepsin structure.png |
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| verifiedrevid = 387635110 |
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| alt = Skeletal formula of (1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetrazabicyclotricos-16-ene-3,6,9,19,22-pentone |
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| IUPAC_name = (1''S'',4''S'',7''Z'',10''S'',16''E'',21''R'')-7-Ethylidene-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetrazabicyclotricos-16-ene-3,6,9,19,22-pentone |
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| CAS_number = 128517-07-7 |
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| image = Romidepsin.svg |
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| synonyms = FK228; FR901228; Istodax |
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| width = 150 |
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| ATC_prefix = none |
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| alt = Skeletal formula of romidepsin |
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| ATC_suffix = |
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| image2 = Romidepsin ball and spoke.png |
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| PubChem = 5352062 |
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| DrugBank = |
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<!--Clinical data--> |
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| ChemSpider = 4509020 |
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| tradename = Istodax |
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| C=24|H=36|N=4|O=6|S=2 |
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| MedlinePlus = a610005 |
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| molecular_weight = 540.695 g/mol |
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| licence_US = Romidepsin |
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| bioavailability = Not applicable (IV only) |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| protein_bound = 92–94% |
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| pregnancy_category = |
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| metabolism = ] (mostly ]-mediated) |
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| elimination_half-life = 3 hours |
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| excretion = |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_US = D |
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| pregnancy_category= |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
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| legal_US = Rx-only |
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| routes_of_administration = ] |
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| routes_of_administration = ] |
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| ATC_prefix = L01 |
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| licence_US = Romidepsin |
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| ATC_suffix = XH02 |
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}} |
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| legal_AU = S4 |
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'''Romidepsin''' (], trade name '''Istodax'''), codenamed '''FK228''' and '''FR901228''', is an ] undergoing ]s as a treatment for ] (CTCL), ], and a variety of other cancers. Romidepsin is a ] obtained from the bacteria '']'', and works by blocking enzymes known as ]s and inducing ] in tumor cells.<ref name=NCI/> It is sometimes referred to as ], after the class of molecules to which it belongs. |
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| legal_AU_comment = <ref>{{cite web | title=Romidepsin-MSN, Romidepsin-Reach (Reach Pharmaceuticals Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=13 January 2023 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/romidepsin-msn-romidepsin-reach-reach-pharmaceuticals-pty-ltd | access-date=29 April 2023 | archive-date=18 March 2023 | archive-url=https://web.archive.org/web/20230318043457/https://www.tga.gov.au/resources/prescription-medicines-registrations/romidepsin-msn-romidepsin-reach-reach-pharmaceuticals-pty-ltd | url-status=live }}</ref> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
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| legal_US = Rx-only |
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<!--Pharmacokinetic data--> |
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| bioavailability = Not applicable (IV only) |
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| protein_bound = 92–94% |
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| metabolism = ] (mostly ]-mediated) |
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| elimination_half-life = 3 hours |
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| excretion = |
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<!--Identifiers--> |
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| IUPHAR_ligand = 7006 |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = 128517-07-7 |
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| PubChem = 5352062 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB06176 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 61080 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = CX3T89XQBK |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 1213490 |
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| ChemSpiderID = 10122002 |
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<!--Chemical data--> |
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| C=24 | H=36 | N=4 | O=6 | S=2 |
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| smiles = C/C=C\1/C(=O)N(C(=O)O\2CC(=O)N(C(=O)N(CSSCC/C=C2)C(=O)N1)C(C)C)C(C)C |
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| StdInChI = 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 |
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| StdInChIKey = OHRURASPPZQGQM-GCCNXGTGSA-N |
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| synonyms = FK228; FR901228; Istodax |
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}} |
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'''Romidepsin''', sold under the brand name '''Istodax''', is an ] used in ] (CTCL) and other ]s (PTCLs). Romidepsin is a ] obtained from the bacterium '']'', and works by blocking enzymes known as ]s, thus inducing ].<ref name=NCI/> It is sometimes referred to as ], after the class of molecules to which it belongs. Romidepsin is branded and owned by Gloucester Pharmaceuticals, a part of ].<ref name=Gloucester/> |
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Romidepsin is branded and owned by Gloucester Pharmaceuticals, now a part of ].<ref name=Gloucester/> On November 5, 2009, it was approved by the ] for the treatment of CTCL, after five years in the agency's ]. |
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==History== |
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==History== |
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===Clinical trials=== |
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===Clinical trials=== |
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] studies of romidepsin began in 1997, sponsored by the ].<ref name=Masuoka/> |
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] studies of romidepsin, initially codenamed FK228 and FR901228, began in 1997.<ref name=Masuoka/> ] and phase III trials were conducted for a variety of indications. The most significant results were found in the treatment of ] (CTCL) and other ]s (PTCLs).<ref name=Masuoka/> |
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In 2004, romidepsin received ] designation from the FDA for the treatment of cutaneous T-cell lymphoma, and ] status from the FDA and the ] for the same indication.<ref name=Masuoka/> |
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] trials were conducted for a variety of indications, including ], ], ],<ref name=Masuoka/> ],<ref name=NCT00098397/> ],<ref name=NCT00085527/> ],<ref name=NCT00104884/> ]s,<ref name=NCT00084461/> and ]s.<ref name=NCT00062075/> |
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The most dramatic results were found in the treatment of ] (CTCL) and other ]s (PTCLs).<ref name=Masuoka/> |
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The FDA approved romidepsin for CTCL in November 2009<ref>{{cite web | url=http://chembl.blogspot.com/2009/11/new-drug-approvals-pt-xxiii-romidepsin.html | title=New Drug Approvals - Pt. XXII - Romidepsin (Istodax) | access-date=2009-12-03 | archive-date=2016-03-03 | archive-url=https://web.archive.org/web/20160303170238/http://chembl.blogspot.com/2009/11/new-drug-approvals-pt-xxiii-romidepsin.html | url-status=live }}</ref> and approved romidepsin for other ]s (PTCLs) in June 2011.<ref>{{cite web | url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Reports.MonthlyApprovalsAll | title=Drugs@FDA: FDA-Approved Drugs | access-date=2015-08-31 | archive-date=2013-07-24 | archive-url=https://web.archive.org/web/20130724043756/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Reports.MonthlyApprovalsAll | url-status=live }}</ref> |
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In 2004, romidepsin received ] designation from the FDA for the treatment of cutaneous T-cell lymphoma, and ] status from the FDA and the ] for the same indication;<ref name=Masuoka/> FDA approval was obtained on November 5, 2009.<ref>http://chembl.blogspot.com/2009/11/new-drug-approvals-pt-xxiii-romidepsin.html</ref> |
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A randomised, phase III trial of romidepsin + ] chemotherapy vs CHOP chemotherapy for patients with ] returned negative results, having no significant impact on progression free survival or overall survival.<ref>{{cite web | url=https://ash.confex.com/ash/2020/webprogram/Paper134440.html | title=Final Analysis of the Ro-CHOP Phase III Study (Conducted by LYSA): Romidepsin Plus CHOP in Patients with Peripheral T-Cell Lymphoma | date=5 December 2020 | access-date=21 May 2021 | archive-date=21 May 2021 | archive-url=https://web.archive.org/web/20210521131009/https://ash.confex.com/ash/2020/webprogram/Paper134440.html | url-status=live }}</ref> |
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As of November 2009, 3 phase II trials for multiple myeloma and peripheral T-cell lymphoma are still recruiting.<ref name=NCT00765102/><ref name=NCT00426764/><ref name=NCT00924378/> |
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==Mechanism of action== |
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===Pre-clinical HIV study=== |
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In 2014, ] published a study involving romidepsin in a trial designed to reactivate latent HIV virus in order to deplete the HIV reservoir. Latently infected ]s were exposed ] and ] to romidepsin, leading to an increase in detectable levels of cell-associated HIV RNA. The trial also compared the effect of romidepsin to another histone deacetylase inhibitor, ]<ref name=Wei>{{cite journal | vauthors = Wei DG, Chiang V, Fyne E, Balakrishnan M, Barnes T, Graupe M, Hesselgesser J, Irrinki A, Murry JP, Stepan G, Stray KM, Tsai A, Yu H, Spindler J, Kearney M, Spina CA, McMahon D, Lalezari J, Sloan D, Mellors J, Geleziunas R, Cihlar T | display-authors = 6 | title = Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing | journal = PLOS Pathogens | volume = 10 | issue = 4 | pages = e1004071 | date = April 2014 | pmid = 24722454 | pmc = 3983056 | doi = 10.1371/journal.ppat.1004071 | doi-access = free }}</ref> |
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Romidepsin acts as a ] with the ] undergoing ] within the cell to release a zinc-binding ].<ref name=Ueda/><ref name=Shigematsu>{{cite journal | author = Shigematsu, N.; Ueda, H.; Takase, S.; Tanaka, H.; Yamamoto, K.; Tada, T. | journal = J. Antibiot. | year = 1994 | volume = 47 | pages = 311–314 | pmid = 8175483 | title = FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. II. Structure determination. | issue = 3}}</ref><ref name=Ueda2>{{cite journal | author = Ueda, H.; Manda, T.; Matsumoto, S.; Mukumoto, S.; Nishigaki, F.; Kawamura, I.; Shimomura, K. | journal = J. Antibiot. | year = 1994 | volume = 47 | pages = 315–323 | pmid = 8175484 | title = FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice. | issue = 3}}</ref> The thiol reversibly interacts with a zinc atom in the binding pocket of Zn-dependent ]. ]s are potential treatments for cancer through the ability to restore normal expression of genes, which may result in cell cycle arrest, differentiation, and ].<ref>{{cite journal | title = Improved Total Synthesis of the Potent HDAC Inhibitor FK228 (FR-901228)| author = Greshock, Thomas J.; Johns, Deidre M.; Noguchi, Yasuo; Williams, Robert M. | journal = Organic Letters | year = 2008 | volume = 10 | issue = 4 | pages = 613–616 | doi = 10.1021/ol702957z | pmid = 18205373}} </ref> |
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===Autism study in animal model=== |
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==Adverse effects== |
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A study involving romidepsin in an animal study that showed that a brief treatment with low amounts of romidepsin could reverse social deficits in a mouse model of autism.<ref name=qin>{{cite journal | vauthors = Qin L, Ma K, Wang ZJ, Hu Z, Matas E, Wei J, Yan Z | title = Social deficits in Shank3-deficient mouse models of autism are rescued by histone deacetylase (HDAC) inhibition | journal = Nature Neuroscience | volume = 21 | issue = 4 | pages = 564–575 | date = April 2018 | pmid = 29531362 | pmc = 5876144 | doi = 10.1038/s41593-018-0110-8 }}</ref> |
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The use of romidepsin is uniformly associated with ].<ref name=label/> In clinical trials, the most common were ] and ], ], ], ], and blood disorders (including ], ], and ]). It has also been associated with metabolic disturbances (such as abnormal ] levels), skin reactions, ], and changes in ].<ref name=label/> |
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== Pharmacodynamics == |
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==References== |
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In a Phase II trial of romidepsin involving patients with CTCL or PTCL, there was evidence of increased histone acetylation in peripheral blood mononuclear cells (PBMCs) extending 4–48 hours. Expression of the ABCB1 gene, a marker of romidepsin-induced gene expression, was also increased in both PBMCs and tumor biopsy samples. Increased gene expression following increased histone acetylation is an expected effect of an HDAC inhibitor. Increased hemoglobin F (another surrogate marker for gene-expression changes resulting from HDAC inhibition) was also detected in blood after romidepsin administration, and persistent histone acetylation was inversely associated with drug clearance and directly associated with patient response to therapy.<ref>{{cite journal | vauthors = Bates SE, Zhan Z, Steadman K, Obrzut T, Luchenko V, Frye R, Robey RW, Turner M, Gardner ER, Figg WD, Steinberg SM, Ling A, Fojo T, To KW, Piekarz RL | display-authors = 6 | title = Laboratory correlates for a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphoma | journal = British Journal of Haematology | volume = 148 | issue = 2 | pages = 256–267 | date = January 2010 | pmid = 19874311 | pmc = 2838427 | doi = 10.1111/j.1365-2141.2009.07954.x }}</ref> |
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{{reflist|colwidth=30em|refs= |
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== Dosage and administration == |
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<ref name=NCI>{{cite web|url=http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=42600|title=Romidepsin|publisher=National Cancer Institute|accessdate=2009-09-11}}</ref> |
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The approved dosage of romidepsin in both CTCL and PTCL is a four-hour i.v. administration of 14 mg/m2 on days 1, 8, and 15 of a 28-day treatment cycle.<ref name=Nakajima /> This cycle should be repeated as long as the patient continues to benefit and tolerate the therapy. A dose reduction to 10 mg/m2 is possible in some patients who experience high-grade toxicities. |
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== Pharmacokinetics == |
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<ref name=Gloucester>{{cite web|url=http://www.gloucesterpharma.com/Romidepsin/Overview.htm|title=Romidepsin|publisher=Gloucester Phamaceuticals|accessdate=2009-09-11}}</ref> |
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In trials involving patients with advanced cancers, romidepsin exhibited linear pharmacokinetics across doses ranging from 1.0 to 24.9 mg/m2 when administered intravenously over four hours.<ref>{{cite journal | vauthors = Bradner JE, West N, Grachan ML, Greenberg EF, Haggarty SJ, Warnow T, Mazitschek R | title = Chemical phylogenetics of histone deacetylases | journal = Nature Chemical Biology | volume = 6 | issue = 3 | pages = 238–243 | date = March 2010 | pmid = 20139990 | pmc = 2822059 | doi = 10.1038/nchembio.313 }}</ref> Age, race, sex, mild-to-severe renal impairment, and mild-to-moderate hepatic impairment had no effect on romidepsin pharmacokinetics. No accumulation of plasma concentration was observed after repeated dosing.<ref name=Nakajima /> |
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==Mechanism of action== |
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<ref name=Ueda>{{cite journal |author=Ueda H, Nakajima H, Hori Y, ''et al.'' |title=FR901228, a novel antitumor bicyclic depsipeptide produced by ''Chromobacterium violaceum'' No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity |journal=Journal of Antibiotics |volume=47 |issue=3 |pages=301–10 |year=1994 |month=March |pmid=7513682}}</ref> |
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Romidepsin acts as a ] with the ] undergoing ] within the cell to release a zinc-binding ].<ref name=Ueda/><ref name=Shigematsu>{{cite journal | vauthors = Shigematsu N, Ueda H, Takase S, Tanaka H, Yamamoto K, Tada T | title = FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. II. Structure determination | journal = The Journal of Antibiotics | volume = 47 | issue = 3 | pages = 311–314 | date = March 1994 | pmid = 8175483 | doi = 10.7164/antibiotics.47.311 | doi-access = free }}</ref><ref name=Ueda2>{{cite journal | vauthors = Ueda H, Manda T, Matsumoto S, Mukumoto S, Nishigaki F, Kawamura I, Shimomura K | title = FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice | journal = The Journal of Antibiotics | volume = 47 | issue = 3 | pages = 315–323 | date = March 1994 | pmid = 8175484 | doi = 10.7164/antibiotics.47.315 | doi-access = free }}</ref> The thiol binds to a zinc atom in the binding pocket of Zn-dependent ] to block its activity. Thus it is an ]. Many ]s are potential treatments for cancer through the ability to epigenetically restore normal expression of tumor suppressor genes, which may result in cell cycle arrest, differentiation, and ].<ref>{{cite journal | vauthors = Greshock TJ, Johns DM, Noguchi Y, Williams RM | title = Improved total synthesis of the potent HDAC inhibitor FK228 (FR-901228) | journal = Organic Letters | volume = 10 | issue = 4 | pages = 613–616 | date = February 2008 | pmid = 18205373 | pmc = 3097137 | doi = 10.1021/ol702957z }}</ref> |
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==Adverse effects== |
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<ref name=Li>{{cite journal |author=Li KW, Wu J, Xing W, Simon JA |title=Total synthesis of the antitumor depsipeptide FR-901,228 |journal=] |volume=118 |issue=30 |pages=7237–8 |year=1996 |month=July |doi=10.1021/ja9613724}}</ref> |
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The use of romidepsin is uniformly associated with ].<ref name=label/> In clinical trials, the most common were ] and ], ], ], ], and blood disorders (including ], ], and ]). It has also been associated with infections, and with metabolic disturbances (such as abnormal ] levels), skin reactions, ], and changes in ].<ref name=label/> |
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== References == |
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<ref name=Nakajima>{{cite journal |author=Nakajima H, Kim YB, Terano H, Yoshida M, Horinouchi S |title=FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor |journal=Experimental Cell Research |volume=241 |issue=1 |pages=126–33 |year=1998 |month=May |pmid=9633520 |doi=10.1006/excr.1998.4027}}</ref> |
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{{reflist|refs= |
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<ref name=NCI>{{cite web|url=http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=42600|title=Romidepsin|publisher=National Cancer Institute|access-date=2009-09-11|archive-date=2009-05-09|archive-url=https://web.archive.org/web/20090509221554/http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=42600|url-status=live}}</ref> |
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<ref name=Masuoka>{{cite book |author=Masuoka Y, Shindoh N, Inamura N |chapter=Histone deacetylase inhibitors from microorganisms: the Astellas experience |editors=Petersen F, Amstutz R |title=Natural compounds as drugs |volume=2 |year=2008 |location=Basel |publisher=Birkhäuser |pages=335–59 |isbn=978-3-7643-8594-1 |url=http://books.google.com/?id=c5vigDmiUiAC}} Retrieved on November 8, 2009 through ].</ref> |
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<ref name=Gloucester>{{cite web|url=http://www.gloucesterpharma.com/Romidepsin/Overview.htm|title=Romidepsin|publisher=Gloucester Pharmaceuticals|access-date=2009-09-11}}{{dead link|date=March 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> |
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<ref name=NCT00098397>{{ClinicalTrialsGov|NCT00098397}}. Retrieved on November 8, 2009.</ref> |
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<ref name=Ueda>{{cite journal | vauthors = Ueda H, Nakajima H, Hori Y, Fujita T, Nishimura M, Goto T, Okuhara M | title = FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity | journal = The Journal of Antibiotics | volume = 47 | issue = 3 | pages = 301–310 | date = March 1994 | pmid = 7513682 | doi = 10.7164/antibiotics.47.301 | doi-access = free }}</ref> |
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<ref name=NCT00085527>{{ClinicalTrialsGov|NCT00085527}}. Retrieved on November 8, 2009.</ref> |
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<ref name=Li>{{cite journal |vauthors=Li KW, Wu J, Xing W, Simon JA |title=Total synthesis of the antitumor depsipeptide FR-901,228 |journal=] |volume=118 |issue=30 |pages=7237–8 |date=July 1996 |doi=10.1021/ja9613724|bibcode=1996JAChS.118.7237L }}</ref> |
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<ref name=NCT00104884>{{ClinicalTrialsGov|NCT00104884}}. Retrieved on November 8, 2009.</ref> |
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<ref name=Nakajima>{{cite journal | vauthors = Nakajima H, Kim YB, Terano H, Yoshida M, Horinouchi S | title = FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor | journal = Experimental Cell Research | volume = 241 | issue = 1 | pages = 126–133 | date = May 1998 | pmid = 9633520 | doi = 10.1006/excr.1998.4027 }}</ref> |
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<ref name=NCT00084461>{{ClinicalTrialsGov|NCT00084461}}. Retrieved on November 8, 2009.</ref> |
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<ref name=Masuoka>{{cite book |vauthors=Masuoka Y, Shindoh N, Inamura N |chapter=Histone deacetylase inhibitors from microorganisms: the Astellas experience |veditors=Petersen F, Amstutz R |title=Natural compounds as drugs |volume=2 |year=2008 |location=Basel |publisher=Birkhäuser |pages=335–59 |isbn=978-3-7643-8594-1 |url=https://books.google.com/books?id=c5vigDmiUiAC}} Retrieved on November 8, 2009 through ].</ref> |
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<ref name=NCT00062075>{{ClinicalTrialsGov|NCT00062075}}. Retrieved on November 8, 2009.</ref> |
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<ref name=label>{{cite web | title=Istodax- romidepsin kit | work = DailyMed | publisher = U.S. National Library of Medicine | date=30 July 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=03b39d40-90fe-11df-9de6-0002a5d5c51b | access-date=29 April 2023 | archive-date=26 November 2022 | archive-url=https://web.archive.org/web/20221126130652/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=03b39d40-90fe-11df-9de6-0002a5d5c51b | url-status=live }}</ref> |
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<ref name=NCT00765102>{{ClinicalTrialsGov|NCT00765102}}. Retrieved on November 8, 2009.</ref> |
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<ref name=NCT00426764>{{ClinicalTrialsGov|NCT00426764}}. Retrieved on November 8, 2009.</ref> |
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<ref name=NCT00924378>{{ClinicalTrialsGov|NCT00924378}}. Retrieved on November 8, 2009.</ref> |
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<ref name=label>{{cite web |author= |title=ISTODEX Label Information |date=November 2009 |publisher=U.S. Food and Drug Administration |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022393lbl.pdf |accessdate=2009-11-07}}</ref> |
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}} |
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}} |
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==External links== |
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* at ] |
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{{Intracellular chemotherapeutic agents}} |
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{{Intracellular chemotherapeutic agents}} |
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{{HDAC inhibitors}} |
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{{Portal bar | Medicine}} |
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