Identification

Name
Romidepsin
Accession Number
DB06176
Type
Small Molecule
Groups
Approved, Investigational
Description

Romidepsin is a selective inhibitor of histone deacetylase, approved in the US in 2009 for the treatment of cutaneous T-cell lymphoma (CTCL) or/and peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior systemic therapy. These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.

Structure
Thumb
Synonyms
  • chromodax
External IDs
FK 228 / FK-228 / FK228 / FR 901228 / FR-901228 / FR901228 / NSC 630176 / NSC-630176 / NSC630176
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IstodaxKit10 mg/2mLCelgene2010-01-04Not applicableUs
IstodaxKit; Powder, for solution10 mgIntravenousCelgene2014-02-05Not applicableCanada
IstodaxKit10 mg/2mLCelgene2010-01-04Not applicableUs
IstodaxKit10 mg/2mLGloucester Pharmaceuticals, Inc.2009-11-052010-05-28Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RomidepsinKit10 mg/2mLPfizer Laboratories Div Pfizer Inc.2010-01-04Not applicableUs
RomidepsinKit10 mg/2mLTeva Parenteral Medicines, Inc.2018-08-01Not applicableUs
International/Other Brands
istodax
Categories
UNII
CX3T89XQBK
CAS number
128517-07-7
Weight
Average: 540.69
Monoisotopic: 540.207627243
Chemical Formula
C24H36N4O6S2
InChI Key
OHRURASPPZQGQM-QDBHDZETSA-N
InChI
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
IUPAC Name
(1S,4S,7Z,10S,21R)-7-ethylidene-6,9,19,22-tetrahydroxy-4,21-bis(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricosa-5,8,16,19,22-pentaen-3-one
SMILES
[H]\C(C)=C1\N=C(O)[C@@]2([H])CSSCCC([H])=C([H])[C@]([H])(CC(O)=N[C@]([H])(C(C)C)C(O)=N2)OC(=O)[C@@]([H])(N=C1O)C(C)C

Pharmacology

Indication

For the treatment of cutaneous T-cell lymphoma (CTCL) or/and peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior systemic therapy. These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Romidepsin is a prodrug, where it becomes active once taken up into the cell. The active metabolite has a free thiol group, which interacts with zinc ions in the active site of class 1 and 2 HDAC enzymes, resulting in inhibition of its enzymatic activity. Certain tumors have over expressed HDACs and downregulated/mutated histone acetyltransferases. This imbalance of HDAC relative to histone acetyltransferase can lead to a decrease in regulatory genes, ensuing tumorigenesis. Inhibition of HDAC may restore normal gene expression in cancer cells and result in cell cycle arrest and apoptosis.

TargetActionsOrganism
AHistone deacetylase 1
antagonist
inhibitor
Human
AHistone deacetylase 2
antagonist
inhibitor
Human
NHistone deacetylase 4
inhibitor
Human
NHistone deacetylase 6
inhibitor
Human
UMultidrug resistance-associated protein 1Not AvailableHuman
Absorption

Romidepsin exhibited linear pharmacokinetics at standard doses.

Volume of distribution

44.5L

Protein binding

Highly protein bound in plasma (92%-94%)

Metabolism

Romidepsin undergoes extensive hepatic metabolism in vitro primarily by CYP3A4 with minor contribution from CYP3A5, CYP1A1, CYP2B6 and CYP2C19.

Route of elimination
Not Available
Half life

Approximately 3 hours

Clearance

8.4L/h

Toxicity

Risk factor D in pregnancy. It is not known if romidepsin is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother. The majority of patients receiving romidepsin experience nausea, vomiting, and anorexia.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbirateroneThe metabolism of Romidepsin can be decreased when combined with Abiraterone.
AcetaminophenThe serum concentration of Romidepsin can be increased when it is combined with Acetaminophen.
Acetyl sulfisoxazoleThe metabolism of Romidepsin can be decreased when combined with Acetyl sulfisoxazole.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Romidepsin.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Romidepsin.
AlbendazoleThe serum concentration of Romidepsin can be increased when it is combined with Albendazole.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Romidepsin.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Romidepsin.
AlimemazineThe risk or severity of QTc prolongation can be increased when Alimemazine is combined with Romidepsin.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Romidepsin.
Food Interactions
  • Avoid grapefruit juice.

References

Synthesis Reference

Ueda H, Nakajima H, Hori Y, Fujita T, Nishimura M, Goto T, Okuhara M: FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity. J Antibiot (Tokyo). 1994 Mar;47(3):301-10. Pubmed.

General References
  1. VanderMolen KM, McCulloch W, Pearce CJ, Oberlies NH: Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. J Antibiot (Tokyo). 2011 Aug;64(8):525-31. doi: 10.1038/ja.2011.35. Epub 2011 May 18. [PubMed:21587264]
  2. Valdez BC, Brammer JE, Li Y, Murray D, Liu Y, Hosing C, Nieto Y, Champlin RE, Andersson BS: Romidepsin targets multiple survival signaling pathways in malignant T cells. Blood Cancer J. 2015 Oct 16;5:e357. doi: 10.1038/bcj.2015.83. [PubMed:26473529]
External Links
KEGG Drug
D06637
PubChem Compound
57515973
PubChem Substance
310264861
ChemSpider
28499157
ChEBI
61080
ChEMBL
CHEMBL1998981
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Romidepsin
ATC Codes
L01XX39 — Romidepsin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (610 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentHistologically Proven Extranodal NKTcell Lymphoma1
1Active Not RecruitingTreatmentCutaneous T-Cell Lymphoma (CTCL)1
1Active Not RecruitingTreatmentHigh Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements / MYC Positive / Recurrent B-Cell Non-Hodgkin Lymphoma / Recurrent Burkitt Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Follicular Lymphoma / Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements / Recurrent Hodgkin Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma / Refractory B-Cell Non-Hodgkin Lymphoma / Refractory Burkitt Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Follicular Lymphoma / Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements / Refractory Hodgkin Lymphoma / Refractory Mantle Cell Lymphoma / Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma1
1Active Not RecruitingTreatmentRecurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Stage I Cutaneous T-cell Non-Hodgkin Lymphoma / Stage IA Mycosis Fungoides/Sezary Syndrome / Stage IB Mycosis Fungoides/Sezary Syndrome / Stage II Cutaneous T-cell Non-Hodgkin Lymphoma / Stage IIA Mycosis Fungoides/Sezary Syndrome / Stage IIB Mycosis Fungoides/Sezary Syndrome / Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IIIA Mycosis Fungoides/Sezary Syndrome / Stage IIIB Mycosis Fungoides/Sezary Syndrome / Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IVA Mycosis Fungoides/Sezary Syndrome / Stage IVB Mycosis Fungoides/Sezary Syndrome1
1CompletedNot AvailableMalignancies, Hematologic / Malignant Lymphomas2
1CompletedTreatmentBlastic Phase Chronic Myelogenous Leukemia / Childhood Central Nervous System Germ Cell Tumor / Childhood Choroid Plexus Tumor / Childhood Chronic Myelogenous Leukemia / Childhood Craniopharyngioma / Childhood Grade I Meningioma / Childhood Grade II Meningioma / Childhood Grade III Meningioma / Childhood High-grade Cerebral Astrocytoma / Childhood Infratentorial Ependymoma / Childhood Low-grade Cerebral Astrocytoma / Childhood Spinal Cord Neoplasm / Childhood Supratentorial Ependymoma / Chronic Lymphocytic Leukemia (CLL) - Refractory / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Recurrent Childhood Brain Stem Glioma / Recurrent Childhood Cerebellar Astrocytoma / Recurrent Childhood Cerebral Astrocytoma / Recurrent Childhood Ependymoma / Recurrent Childhood Medulloblastoma / Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor / Recurrent Childhood Visual Pathway and Hypothalamic Glioma / Relapsing Chronic Myelogenous Leukemia / Unspecified Childhood Solid Tumor, Protocol Specific1
1CompletedTreatmentChronic Myeloproliferative Disorders / Leukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentLeukemias / Malignant Lymphomas2
1CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL) / Peripheral T-Cell Lymphoma (PTCL)1
1CompletedTreatmentMalignant Lymphomas1
1CompletedTreatmentMalignant Neoplasm of Pancreas1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentTumors, Solid / Virally Mediated Cancers and Liposarcoma1
1Not Yet RecruitingTreatmentBreast Adenocarcinoma / Recurrent Breast Carcinoma / Recurrent Hodgkin Lymphoma / Recurrent Mycosis Fungoides / Recurrent Non-Hodgkin Lymphoma / Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Refractory Hodgkin Lymphoma / Refractory Nodal Marginal Zone Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory, advanced Mycosis fungoides / Refractory, primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IV Breast Cancer AJCC v6 and v71
1RecruitingTreatmentAdult Mixed Glioma / Adult Pineal Gland Astrocytoma / Adult Solid Neoplasm / AIDS Related Immunoblastic Lymphoma / AIDS-Related Burkitt Lymphoma / AIDS-Related Diffuse Large Cell Lymphoma / AIDS-Related Diffuse Mixed Cell Lymphoma / AIDS-Related Diffuse Small Cleaved Cell Lymphoma / AIDS-Related Hodgkin Lymphoma / AIDS-Related Lymphoblastic Lymphoma / AIDS-Related Primary Central Nervous System Lymphoma / Chronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Gliomas / Lymphoma, AIDS Related / Malignant Lymphomas / Metastatic Malignant Solid Neoplasm / Metastatic Solid Neoplasm / Neuroendocrine Neoplasms / Recurrent Adult Brain Neoplasm / Recurrent Adult Soft Tissue Sarcoma / Recurrent Bladder Carcinoma / Recurrent Breast Carcinoma / Recurrent Colorectal Carcinoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Head and Neck Carcinoma / Recurrent Lung Carcinoma / Recurrent Malignant Solid Neoplasm / Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma / Recurrent Melanoma / Recurrent Pancreatic Carcinoma / Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Prostate Carcinoma / Recurrent Solid Neoplasm / Recurrent Thyroid Gland Carcinoma / Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma / Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma / Refractory, primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Renal Cell Carcinoma Recurrent / Stage III Breast Cancer / Stage III Breast Cancer AJCC V7 / Stage III Colorectal Cancer / Stage III Colorectal Cancer AJCC v7 / Stage III Cutaneous Melanoma AJCC v7 / Stage III Lung Cancer / Stage III Lung Cancer AJCC v7 / Stage III Pancreatic Cancer / Stage III Pancreatic Cancer AJCC v6 and v7 / Stage III Prostate Cancer / Stage III Prostate Cancer AJCC v7 / Stage III Renal Cell Cancer / Stage III Renal Cell Cancer AJCC v7 / Stage III Soft Tissue Sarcoma / Stage III Soft Tissue Sarcoma AJCC v7 / Stage IIIA Breast Cancer / Stage IIIA Breast Cancer AJCC v7 / Stage IIIA Colorectal Cancer / Stage IIIA Colorectal Cancer AJCC v7 / Stage IIIA Cutaneous Melanoma AJCC v7 / Stage IIIA Skin Melanoma / Stage IIIB Breast Cancer / Stage IIIB Breast Cancer AJCC v7 / Stage IIIB Colorectal Cancer / Stage IIIB Colorectal Cancer AJCC v7 / Stage IIIB Cutaneous Melanoma AJCC v7 / Stage IIIB Skin Melanoma / Stage IIIC Breast Cancer / Stage IIIC Breast Cancer AJCC v7 / Stage IIIC Colorectal Cancer / Stage IIIC Colorectal Cancer AJCC v7 / Stage IIIC Cutaneous Melanoma AJCC v7 / Stage IIIC Skin Melanoma / Stage IV Breast Cancer / Stage IV Breast Cancer AJCC v6 and v7 / Stage IV Colorectal Cancer / Stage IV Colorectal Cancer AJCC v7 / Stage IV Cutaneous Melanoma AJCC v6 and v7 / Stage IV Lung Cancer / Stage IV Lung Cancer AJCC v7 / Stage IV Pancreatic Cancer / Stage IV Pancreatic Cancer AJCC v6 and v7 / Stage IV Prostate Cancer / Stage IV Prostate Cancer AJCC v7 / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V7 / Stage IV Skin Melanoma / Stage IV Soft Tissue Sarcoma / Stage IV Soft Tissue Sarcoma AJCC v7 / Stage IVA Colorectal Cancer / Stage IVA Colorectal Cancer AJCC v7 / Stage IVB Colorectal Cancer / Stage IVB Colorectal Cancer AJCC v7 / Stages III Skin Melanoma / Unresectable Solid Neoplasm1
1RecruitingTreatmentColorectal Cancers1
1RecruitingTreatmentCutaneous Lymphomas / Malignant Lymphomas / T-Cell Lymphomas1
1RecruitingTreatmentCutaneous T-Cell Lymphoma (CTCL)1
1RecruitingTreatmentCutaneous T-Cell Lymphoma (CTCL) / Peripheral T-Cell Lymphoma (PTCL) / T-Large Granulocytic Leukemia / T-Lymphoblastic Leukemia/Lymphoma / T-Prolymphocytic Leukemia1
1RecruitingTreatmentHodgkins Disease (HD) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Lymphoma, T-Cell, Cutaneous / Lymphoma, T-Cell, Peripheral1
1RecruitingTreatmentMalignant Lymphomas / Relapsed/Refractory T-cell Lymphomas1
1TerminatedTreatmentCutaneous T-Cell Lymphoma (CTCL) / Mycosis Fungoides (MF) / Neoplasms1
1WithdrawnTreatmentCTCL / PTCL1
1, 2Active Not RecruitingTreatmentLymphoma, T-Cell, Peripheral1
1, 2Active Not RecruitingTreatmentMultiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
1, 2Active Not RecruitingTreatmentRelapsed or Refractory / Relapsed or Refractory B- / T-Cell Lymphomas1
1, 2CompletedTreatmentAdult Anaplastic Astrocytoma / Adult Anaplastic Oligodendroglioma / Adult Giant Cell Glioblastoma / Adult Gliosarcoma / Adult Mixed Glioma / Recurrent Adult Brain Tumor1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2CompletedTreatmentLung Cancers / Metastatic Cancers1
1, 2CompletedTreatmentPeripheral T Cell Lymphoma (PTCL)1
1, 2Not Yet RecruitingTreatmentLymphoma, T-Cell, Peripheral1
1, 2RecruitingTreatmentALK- Anaplastic Large Cell Lymphoma (ALCL) / ALK- Anaplastic Largecell Lymphoma (ALCL) / Angioimmunoblastic T-cell Lymphoma (AITL) / Peripheral T-Cell Lymphoma (PTCL) / Peripheral T-cell Lymphomas Not Otherwise Specified (PTCL-NOS) / PTCL-NOS1
1, 2RecruitingTreatmentCancer, Breast / Triple-Negative Breast Cancer (TNBC)1
1, 2RecruitingTreatmentCutaneous T-Cell Lymphoma (CTCL) / Lymphoid Haematopoietic / Neoplasms, Malignant / Refractory peripheral cutaneous T-cell lymphoma1
1, 2RecruitingTreatmentLymphoid Malignancies / Lymphoma, Hodgkins / Malignant Lymphomas / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
1, 2RecruitingTreatmentLymphoid Malignancies / Lymphoma, Hodgkins / Malignant Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
1, 2RecruitingTreatmentPeripheral T Cell Lymphoma (PTCL)1
1, 2RecruitingTreatmentT-Cell Lymphomas1
1, 2TerminatedTreatmentHER2-Negative Breast Cancer / Inflammatory carcinoma of the breast / Male Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
1, 2TerminatedTreatmentLymphoma, Hodgkins / Mature T-cell Lymphoma / Multiple Myeloma (MM)1
1, 2TerminatedTreatmentMultiple Myeloma (MM)1
1, 2Unknown StatusTreatmentChronic HIV-infection1
1, 2Unknown StatusTreatmentMultiple Myeloma (MM)1
1, 2WithdrawnTreatmentB-cell Adult Acute Lymphoblastic Leukemia / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Small Lymphocytic Lymphoma / Refractory Hairy Cell Leukemia / Small Intestine Lymphoma / Splenic Marginal Zone Lymphoma / Testicular Lymphoma / Waldenström's Macroglobulinemia (WM)1
2Active Not RecruitingTreatmentAdult Alveolar Soft-part Sarcoma / Adult Angiosarcoma / Adult Epithelioid Sarcoma / Adult Extraskeletal Chondrosarcoma / Adult Extraskeletal Osteosarcoma / Adult Fibrosarcoma / Adult Leiomyosarcoma / Adult Liposarcoma / Adult Malignant Fibrous Histiocytoma / Adult Malignant Hemangiopericytoma / Adult Malignant Mesenchymoma / Adult Neurofibrosarcoma / Adult Rhabdomyosarcoma / Adult Synovial Sarcoma / Gastrointestinal Stromal Tumors / Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Adult Soft Tissue Sarcoma / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma1
2Active Not RecruitingTreatmentCutaneous T Cell Lymphomas (CTCL) / Peripheral T Cell Lymphoma (PTCL)1
2Active Not RecruitingTreatmentPeripheral T-Cell Lymphoma (PTCL)1
2CompletedTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Promyelocytic Leukemia (M3) / Recurrent Adult Acute Myeloid Leukemia1
2CompletedTreatmentCancers / Malignant Lymphomas1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL)1
2CompletedTreatmentDS Stage II Plasma Cell Myeloma / DS Stage III Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
2CompletedTreatmentExtensive Stage Small Cell Lung Cancer / Non-Small Cell Lung Cancer Recurrent / Refractory Small cell lung cancer / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIb Non-small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer1
2CompletedTreatmentLeukemias / Malignant Lymphomas / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms1
2CompletedTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentMetastases / Prostate Cancer1
2CompletedTreatmentNeoplasms Metastasis / Renal Cell Adenocarcinoma1
2CompletedTreatmentPeripheral T-Cell Lymphoma (PTCL)1
2CompletedTreatmentProstatic Neoplasms / Renal Cell Adenocarcinoma1
2CompletedTreatmentRecurrent Thyroid Cancer / Stage IV Follicular Thyroid Cancer / Stage IV Papillary Thyroid Cancer1
2CompletedTreatmentStage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Larynx / Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IV Squamous Cell Carcinoma of the Oropharynx1
2CompletedTreatmentRefractory Small cell lung cancer1
2RecruitingTreatmentAdult Nasal Type Extranodal NK/T-Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Hepatosplenic T-Cell Lymphoma / Peripheral T-Cell Lymphoma (PTCL) / Stage I Cutaneous T-cell Non-Hodgkin Lymphoma / Stage IA Mycosis Fungoides/Sezary Syndrome / Stage IB Mycosis Fungoides/Sezary Syndrome / Stage II Cutaneous T-cell Non-Hodgkin Lymphoma / Stage IIA Mycosis Fungoides/Sezary Syndrome / Stage IIB Mycosis Fungoides/Sezary Syndrome / Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IIIA Mycosis Fungoides/Sezary Syndrome / Stage IIIB Mycosis Fungoides/Sezary Syndrome / Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IVA Mycosis Fungoides/Sezary Syndrome / Stage IVB Mycosis Fungoides/Sezary Syndrome1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV)2
2TerminatedTreatmentAdenocarcinoma of the Esophagus / Adenocarcinoma of the Stomach / Recurrent Esophageal Cancer / Recurrent Gastric Cancer1
2TerminatedTreatmentBladder Cancers / Transitional Cell Cancer of the Renal Pelvis and Ureter / Urethral Cancer1
2TerminatedTreatmentGastrinoma / Glucagonoma / Insulinoma / Metastatic Gastrointestinal Carcinoid Tumor / Pancreatic Polypeptide Tumor / Pulmonary Carcinoid Tumor / Recurrent Gastrointestinal Carcinoid Tumor / Recurrent Islet Cell Carcinoma / Regional Gastrointestinal Carcinoid Tumor / Somatostatinoma1
2TerminatedTreatmentMalignant Melanoma / Melanoma1
2TerminatedTreatmentMultiple Myeloma (MM)1
2TerminatedTreatmentPrimary Peritoneal Cavity Cancer / Recurrent Ovarian Epithelial Cancer1
2TerminatedTreatmentRecurrent Adult Diffuse Large Cell Lymphoma / Recurrent Mantle Cell Lymphoma1
2TerminatedTreatmentRecurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Small Lymphocytic Lymphoma1
2WithdrawnTreatmentCancer of the Ovary1
3Active Not RecruitingTreatmentPeripheral T-Cell Lymphoma (PTCL)1
3CompletedTreatmentRefractory Peripheral T-cell Lymphoma Unspecified / Relapsed Peripheral T-Cell Lymphoma1
3Not Yet RecruitingOtherLymphoma, T-Cell, Peripheral1
3Not Yet RecruitingTreatmentRefractory Angioimmunoblastic T-cell Lymphoma / Relapsed Angioimmunoblastic T-Cell Lymphoma1
Not AvailableCompletedNot AvailableCutaneous T-Cell Lymphoma (CTCL)1
Not AvailableTerminatedSupportive CareGraft Versus Host Disease (GVHD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit10 mg/2mL
Kit; powder, for solutionIntravenous10 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7611724No2001-08-222021-08-22Us
US7608280No2001-08-222021-08-22Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.021 mg/mLALOGPS
logP3.05ALOGPS
logP-0.53ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)-9.5ChemAxon
pKa (Strongest Basic)14.95ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area156.66 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity144.17 m3·mol-1ChemAxon
Polarizability54.56 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as cyclic depsipeptides. These are natural or synthetic compounds having sequences of amino and hydroxy carboxylic acid residues (usually α-amino and α-hydroxy acids) connected in a ring. The residues are commonly but not necessarily regularly alternating.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Depsipeptides
Direct Parent
Cyclic depsipeptides
Alternative Parents
Macrolide lactams / Alpha amino acid esters / Macrolides and analogues / Macrolactams / Secondary carboxylic acid amides / Carboxylic acid esters / Organic disulfides / Lactones / Lactams / Oxacyclic compounds
show 7 more
Substituents
Cyclic depsipeptide / Macrolide lactam / Alpha-amino acid ester / Macrolactam / Macrolide / Alpha-amino acid or derivatives / Carboxamide group / Carboxylic acid ester / Lactam / Lactone
show 16 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Transcription regulatory region sequence-specific dna binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC1
Uniprot ID
Q13547
Uniprot Name
Histone deacetylase 1
Molecular Weight
55102.615 Da
References
  1. VanderMolen KM, McCulloch W, Pearce CJ, Oberlies NH: Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. J Antibiot (Tokyo). 2011 Aug;64(8):525-31. doi: 10.1038/ja.2011.35. Epub 2011 May 18. [PubMed:21587264]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Transcription factor binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC2
Uniprot ID
Q92769
Uniprot Name
Histone deacetylase 2
Molecular Weight
55363.855 Da
References
  1. VanderMolen KM, McCulloch W, Pearce CJ, Oberlies NH: Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. J Antibiot (Tokyo). 2011 Aug;64(8):525-31. doi: 10.1038/ja.2011.35. Epub 2011 May 18. [PubMed:21587264]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC4
Uniprot ID
P56524
Uniprot Name
Histone deacetylase 4
Molecular Weight
119038.875 Da
References
  1. VanderMolen KM, McCulloch W, Pearce CJ, Oberlies NH: Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. J Antibiot (Tokyo). 2011 Aug;64(8):525-31. doi: 10.1038/ja.2011.35. Epub 2011 May 18. [PubMed:21587264]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC6
Uniprot ID
Q9UBN7
Uniprot Name
Histone deacetylase 6
Molecular Weight
131418.19 Da
References
  1. VanderMolen KM, McCulloch W, Pearce CJ, Oberlies NH: Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. J Antibiot (Tokyo). 2011 Aug;64(8):525-31. doi: 10.1038/ja.2011.35. Epub 2011 May 18. [PubMed:21587264]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Xiao JJ, Foraker AB, Swaan PW, Liu S, Huang Y, Dai Z, Chen J, Sadee W, Byrd J, Marcucci G, Chan KK: Efflux of depsipeptide FK228 (FR901228, NSC-630176) is mediated by P-glycoprotein and multidrug resistance-associated protein 1. J Pharmacol Exp Ther. 2005 Apr;313(1):268-76. Epub 2005 Jan 5. [PubMed:15634944]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Iwamoto FM, Lamborn KR, Kuhn JG, Wen PY, Yung WK, Gilbert MR, Chang SM, Lieberman FS, Prados MD, Fine HA: A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03. Neuro Oncol. 2011 May;13(5):509-16. doi: 10.1093/neuonc/nor017. Epub 2011 Mar 3. [PubMed:21377994]
  2. Shiraga T, Tozuka Z, Ishimura R, Kawamura A, Kagayama A: Identification of cytochrome P450 enzymes involved in the metabolism of FK228, a potent histone deacetylase inhibitor, in human liver microsomes. Biol Pharm Bull. 2005 Jan;28(1):124-9. [PubMed:15635176]
  3. Woo S, Gardner ER, Chen X, Ockers SB, Baum CE, Sissung TM, Price DK, Frye R, Piekarz RL, Bates SE, Figg WD: Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503. doi: 10.1158/1078-0432.CCR-08-1215. [PubMed:19228751]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Shiraga T, Tozuka Z, Ishimura R, Kawamura A, Kagayama A: Identification of cytochrome P450 enzymes involved in the metabolism of FK228, a potent histone deacetylase inhibitor, in human liver microsomes. Biol Pharm Bull. 2005 Jan;28(1):124-9. [PubMed:15635176]
  2. Woo S, Gardner ER, Chen X, Ockers SB, Baum CE, Sissung TM, Price DK, Frye R, Piekarz RL, Bates SE, Figg WD: Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503. doi: 10.1158/1078-0432.CCR-08-1215. [PubMed:19228751]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Woo S, Gardner ER, Chen X, Ockers SB, Baum CE, Sissung TM, Price DK, Frye R, Piekarz RL, Bates SE, Figg WD: Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503. doi: 10.1158/1078-0432.CCR-08-1215. [PubMed:19228751]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Woo S, Gardner ER, Chen X, Ockers SB, Baum CE, Sissung TM, Price DK, Frye R, Piekarz RL, Bates SE, Figg WD: Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503. doi: 10.1158/1078-0432.CCR-08-1215. [PubMed:19228751]

Drug created on March 19, 2008 10:15 / Updated on September 23, 2018 19:37