trabectedin Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
4633 114899-77-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ecteinascidin 743
  • ET-743
  • ET 743
  • trabectedin
  • yondelis
  • ecteinascidin
  • ecteinascidine
A complex structure that includes isoquinolines joined by a cyclic ester; it is a DNA-binding agent and guanine N2 alkylator derived from the marine tunicate, Ecteinascidia turbinata. Trabectedin is used for the treatment of advanced soft-tissue SARCOMA, after failure of ANTHRACYCLINES or IFOSFAMIDE drug therapy.
  • Molecular weight: 761.84
  • Formula: C39H43N3O11S
  • CLOGP: 2.76
  • LIPINSKI: 2
  • HAC: 14
  • HDO: 4
  • TPSA: 168.72
  • ALOGS: -3.37
  • ROTB: 4

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 25 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 12 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.06 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 44 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Sept. 4, 2015 PMDA
Oct. 23, 2015 FDA JANSSEN PRODS
Sept. 17, 2007 EMA Pharma Mar S.A.

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
Neutropenia 223.99 45.09 122 2419 143082 46540439
Febrile neutropenia 140.18 45.09 78 2463 94549 46588972
Pancytopenia 117.44 45.09 67 2474 84991 46598530
Thrombocytopenia 114.30 45.09 76 2465 126505 46557016
Anaemia 94.96 45.09 91 2450 255688 46427833
Blood creatine phosphokinase increased 89.62 45.09 39 2502 27685 46655836
Alanine aminotransferase increased 79.41 45.09 53 2488 88398 46595123
Aspartate aminotransferase increased 72.65 45.09 48 2493 78652 46604869
Rhabdomyolysis 71.43 45.09 38 2503 41871 46641650
Neutrophil count decreased 56.55 45.09 33 2508 43393 46640128
Leukopenia 54.26 45.09 38 2503 68305 46615216
Acute myeloid leukaemia 47.07 45.09 21 2520 15757 46667764
Capillary leak syndrome 45.20 45.09 12 2529 1885 46681636

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
Haematotoxicity 66.84 45.37 19 1008 6151 29945300
Rhabdomyolysis 62.08 45.37 34 993 63546 29887905
Hepatotoxicity 60.90 45.37 23 1004 18122 29933329
Pancytopenia 57.93 45.37 36 991 85016 29866435
Neutrophil count decreased 53.63 45.37 27 1000 42427 29909024
Alanine aminotransferase increased 51.96 45.37 32 995 74244 29877207
Aspartate aminotransferase increased 51.29 45.37 30 997 63392 29888059

Pharmacologic Action:

SourceCodeDescription
ATC L01CX01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS
Other plant alkaloids and natural products
FDA MoA N0000000236 Alkylating Activity
FDA EPC N0000175558 Alkylating Drug
MeSH PA D000477 Alkylating Agents
MeSH PA D000970 Antineoplastic Agents
MeSH PA D018906 Antineoplastic Agents, Alkylating
MeSH PA D009676 Noxae
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:67079 antiinflammatory agents
CHEBI has role CHEBI:76507 marine metabolites

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Liposarcoma indication 254829001 DOID:3382
Malignant tumor of ovary indication 363443007 DOID:2394
Leiomyosarcoma indication 443719001 DOID:1967
Soft or Connective Tissue Sarcoma indication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.18 acidic
pKa2 10.36 acidic
pKa3 10.93 acidic
pKa4 8.21 Basic
pKa5 7.59 Basic
pKa6 1.0 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
1MG/VIAL YONDELIS JANSSEN PRODS N207953 Oct. 23, 2015 RX POWDER INTRAVENOUS April 23, 2021 PEDIATRIC EXCLUSIVITY
1MG/VIAL YONDELIS JANSSEN PRODS N207953 Oct. 23, 2015 RX POWDER INTRAVENOUS June 29, 2021 INFORMATION ADDED TO SECTION 8.4 OF THE LABELING TO DESCRIBE THE RESULTS FROM PEDIATRIC STUDIES
1MG/VIAL YONDELIS JANSSEN PRODS N207953 Oct. 23, 2015 RX POWDER INTRAVENOUS Dec. 29, 2021 PEDIATRIC EXCLUSIVITY
1MG/VIAL YONDELIS JANSSEN PRODS N207953 Oct. 23, 2015 RX POWDER INTRAVENOUS Oct. 23, 2022 FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC LIPOSARCOMA OR LEIOMYOSARCOMA WHO RECEIVED A PRIOR ANTHRACYCLINE-CONTAINING REGIMEN
1MG/VIAL YONDELIS JANSSEN PRODS N207953 Oct. 23, 2015 RX POWDER INTRAVENOUS April 23, 2023 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proto-oncogene tyrosine-protein kinase Src Kinase IC50 6.68 CHEMBL
DNA DNA ALKYLATING AGENT DRUG LABEL DRUG LABEL
Nuclear receptor subfamily 1 group I member 2 Nuclear hormone receptor ANTAGONIST IC50 8.52 IUPHAR

External reference:

IDSource
D06199 KEGG_DRUG
4035010 VANDF
C0388976 UMLSCUI
CHEBI:84050 CHEBI
ECT PDB_CHEM_ID
CHEMBL297812 ChEMBL_ID
CHEMBL1224207 ChEMBL_ID
CHEMBL450449 ChEMBL_ID
DB05109 DRUGBANK_ID
D000077606 MESH_DESCRIPTOR_UI
108150 PUBCHEM_CID
8206 INN_ID
ID0YZQ2TCP UNII
2774 IUPHAR_LIGAND_ID
1716278 RXNORM
165758 MMSL
26244 MMSL
d07398 MMSL
012537 NDDF
432214004 SNOMEDCT_US
433127001 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
YONDELIS HUMAN PRESCRIPTION DRUG LABEL 1 59676-610 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 0.05 mg INTRAVENOUS NDA 29 sections