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

Stem definitionDrug idCAS RN
ecteinascidin derivatives 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 260.11 45.89 137 2831 174868 63311186
Febrile neutropenia 181.93 45.89 95 2873 118354 63367700
Pancytopenia 163.93 45.89 83 2885 96850 63389204
Thrombocytopenia 139.58 45.89 87 2881 151070 63334984
Anaemia 107.64 45.89 97 2871 293333 63192721
Rhabdomyolysis 105.67 45.89 48 2920 43903 63442151
Blood creatine phosphokinase increased 98.49 45.89 41 2927 30389 63455665
Alanine aminotransferase increased 86.28 45.89 56 2912 103714 63382340
Aspartate aminotransferase increased 75.70 45.89 49 2919 90228 63395826
Leukopenia 72.40 45.89 45 2923 77245 63408809
Acute myeloid leukaemia 65.37 45.89 26 2942 17121 63468933
Neutrophil count decreased 60.93 45.89 36 2932 56370 63429684
Capillary leak syndrome 54.93 45.89 14 2954 2186 63483868
Transaminases increased 50.33 45.89 26 2942 31341 63454713
Lymphangioleiomyomatosis 46.36 45.89 8 2960 184 63485870

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
Rhabdomyolysis 76.26 43.49 41 1258 68122 34887510
Pancytopenia 73.67 43.49 45 1254 95112 34860520
Haematotoxicity 64.15 43.49 20 1279 8174 34947458
Hepatotoxicity 55.29 43.49 23 1276 21462 34934170
Alanine aminotransferase increased 49.45 43.49 33 1266 80782 34874850
Aspartate aminotransferase increased 47.13 43.49 30 1269 67753 34887879
Neutrophil count decreased 46.82 43.49 27 1272 51077 34904555
Transaminases increased 44.16 43.49 21 1278 26802 34928830

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
Pancytopenia 193.40 42.03 111 3627 165634 79575016
Neutropenia 191.48 42.03 135 3603 287575 79453075
Febrile neutropenia 147.87 42.03 106 3632 230893 79509757
Rhabdomyolysis 133.38 42.03 74 3664 103057 79637593
Thrombocytopenia 126.18 42.03 102 3636 265157 79475493
Anaemia 106.86 42.03 117 3621 444898 79295752
Alanine aminotransferase increased 102.43 42.03 74 3664 162496 79578154
Neutrophil count decreased 98.91 42.03 59 3679 93900 79646750
Aspartate aminotransferase increased 91.64 42.03 65 3673 138576 79602074
Leukopenia 89.66 42.03 60 3678 116453 79624197
Haematotoxicity 82.43 42.03 30 3708 15489 79725161
Transaminases increased 80.41 42.03 42 3696 51701 79688949
Hepatotoxicity 75.02 42.03 40 3698 51312 79689338
Platelet count decreased 74.15 42.03 66 3672 194598 79546052
Blood creatine phosphokinase increased 68.19 42.03 41 3697 66049 79674601
Capillary leak syndrome 60.17 42.03 17 3721 3908 79736742
Acute myeloid leukaemia 53.53 42.03 27 3711 30858 79709792
Hepatic function abnormal 52.24 42.03 36 3702 73071 79667579
White blood cell count decreased 51.10 42.03 53 3685 188235 79552415
Device related infection 45.29 42.03 25 3713 34269 79706381
Hypertransaminasaemia 45.10 42.03 18 3720 11906 79728744

FDA Adverse Event Reporting System (Pediatric)

None

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 antineoplastic agents
CHEBI has role CHEBI:67079 anti-inflammatory agents
CHEBI has role CHEBI:76507 marine metabolites

Drug Use | Suggest Off label Use Form| |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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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, 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
Nuclear receptor subfamily 1 group I member 2 Nuclear hormone receptor ANTAGONIST IC50 8.52 IUPHAR

External reference:

IDSource
D06199 KEGG_DRUG
4035010 VANDF
CHEBI:84050 CHEBI
ECT PDB_CHEM_ID
CHEMBL450449 ChEMBL_ID
CHEMBL1224207 ChEMBL_ID
2774 IUPHAR_LIGAND_ID
8206 INN_ID
DB05109 DRUGBANK_ID
ID0YZQ2TCP UNII
1716278 RXNORM
165758 MMSL
26244 MMSL
d07398 MMSL
012537 NDDF
432214004 SNOMEDCT_US
433127001 SNOMEDCT_US
C1311070 UMLSCUI
D000077606 MESH_DESCRIPTOR_UI
108150 PUBCHEM_CID

Pharmaceutical products:

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