romidepsin ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
depsipeptide derivatives 4119 128517-07-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • romidepsin
  • chromadax
  • istodax
  • FR901228
  • FK228
a bicyclic depsipeptide and a potent histone deacetylase inhibitor from Chromobacterium violaceum
  • Molecular weight: 540.69
  • Formula: C24H36N4O6S2
  • CLOGP: 3.44
  • LIPINSKI: 1
  • HAC: 10
  • HDO: 4
  • TPSA: 142.70
  • ALOGS: -4.41
  • ROTB: 2

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.64 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 1.20 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 7.40 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.07 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 11 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 5, 2009 FDA CELGENE
July 3, 2017 PMDA Celgene KK

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Electrocardiogram QT prolonged 92.68 41.84 34 878 59496 63428614
Thrombocytopenia 59.50 41.84 33 879 151124 63336986
Platelet count decreased 58.80 41.84 30 882 116092 63372018
Tumour lysis syndrome 47.17 41.84 13 899 8977 63479133

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 50.51 36.83 35 958 119682 34836256
Thrombocytopenia 48.61 36.83 38 955 156209 34799729

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 103.03 35.88 60 1711 194604 79548013
Thrombocytopenia 85.98 35.88 60 1711 265199 79477418
Pyrexia 50.33 35.88 68 1703 678641 79063976
Tumour lysis syndrome 49.58 35.88 19 1752 23920 79718697
Atrial fibrillation 48.69 35.88 38 1733 197848 79544769
Malignant neoplasm progression 37.55 35.88 28 1743 135962 79606655
Cutaneous T-cell lymphoma 36.17 35.88 9 1762 2694 79739923

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01XH02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Histone deacetylase (HDAC) inhibitors
FDA MoA N0000175071 Histone Deacetylase Inhibitors
FDA EPC N0000175588 Histone Deacetylase Inhibitor
MeSH PA D000903 Antibiotics, Antineoplastic
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D056572 Histone Deacetylase Inhibitors
FDA MoA N0000187061 Organic Cation Transporter 2 Inhibitors
FDA MoA N0000190107 Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA N0000190108 Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA N0000190110 Organic Anion Transporter 1 Inhibitors
FDA MoA N0000193845 Bile Salt Export Pump Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:61115 histone deacetylase inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Peripheral T-cell lymphoma indication 109977009
Primary cutaneous T-cell lymphoma indication 400122007
Hypokalemia contraindication 43339004
Conduction disorder of the heart contraindication 44808001
Lymphocytopenia contraindication 48813009 DOID:614
Leukopenia contraindication 84828003 DOID:615
Chronic renal failure syndrome contraindication 90688005
Prolonged QT interval contraindication 111975006
Acute disease of cardiovascular system contraindication 128487001
Hypomagnesemia contraindication 190855004
Disease of liver contraindication 235856003 DOID:409
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Breastfeeding (mother) contraindication 413712001
Congenital long QT syndrome contraindication 442917000




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.47 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Histone deacetylase Enzyme INHIBITOR Ki 5.96 IUPHAR DRUG LABEL
Histone deacetylase 2 Enzyme IC50 7.33 WOMBAT-PK
Histone deacetylase 1 Enzyme IC50 7 WOMBAT-PK
Histone deacetylase 3 Enzyme Ki 7.60 WOMBAT-PK
Histone deacetylase 6 Enzyme Ki 6.52 WOMBAT-PK
Histone deacetylase 7 Enzyme INHIBITOR Ki 5.90 IUPHAR
Histone deacetylase 8 Enzyme INHIBITOR Ki 9.82 IUPHAR
Histone deacetylase 5 Enzyme INHIBITOR Ki 6.26 IUPHAR
Histone deacetylase 9 Enzyme INHIBITOR Ki 5.96 IUPHAR
Bromodomain-containing protein 4 Unclassified IC50 7.44 CHEMBL
Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) Transcription factor IC50 7.74 CHEMBL
Histone deacetylase 3/NCoR1 Transcription factor Ki 9.82 CHEMBL
Histone deacetylase 4 Enzyme IC50 6.29 WOMBAT-PK
Histone deacetylase 6 Enzyme IC50 6.41 CHEMBL

External reference:

IDSource
4029461 VUID
N0000180306 NUI
D06637 KEGG_DRUG
4029461 VANDF
C1527027 UMLSCUI
CHEBI:61080 CHEBI
CHEMBL343448 ChEMBL_ID
DB06176 DRUGBANK_ID
C087123 MESH_SUPPLEMENTAL_RECORD_UI
7006 IUPHAR_LIGAND_ID
8656 INN_ID
CX3T89XQBK UNII
5352062 PUBCHEM_CID
877436 RXNORM
169125 MMSL
267261 MMSL
26838 MMSL
d07512 MMSL
013396 NDDF
444608004 SNOMEDCT_US
444737005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Romidepsin HUMAN PRESCRIPTION DRUG LABEL 1 0703-4004 INJECTION, SOLUTION, CONCENTRATE 5 mg INTRAVENOUS NDA 29 sections
Romidepsin HUMAN PRESCRIPTION DRUG LABEL 1 0703-4004 INJECTION, SOLUTION, CONCENTRATE 5 mg INTRAVENOUS NDA 29 sections
Romidepsin HUMAN PRESCRIPTION DRUG LABEL 1 0703-4004 INJECTION, SOLUTION, CONCENTRATE 5 mg INTRAVENOUS NDA 29 sections