trabectedin 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2A,ACVR2B,AKT2,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK2,CDK4,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,GRK2,GSK3B,IGF1R,ITK,JAK2,JAK3,MAP2K6,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,MET,MTOR,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ZAP70 53
kinase-selectivity-class ACVR2B,EIF2AK3,GRK2,MAP2K6 4
pfas-class PFAS structural alert (1 = True, 0 = False) 0

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 278.94 46.04 150 3601 224754 90399942
Pancytopenia 203.20 46.04 99 3652 120164 90504532
Febrile neutropenia 180.24 46.04 100 3651 158249 90466447
Thrombocytopenia 169.68 46.04 106 3645 208619 90416077
Anaemia 166.21 46.04 128 3623 352674 90272022
Rhabdomyolysis 136.43 46.04 58 3693 51198 90573498
Blood creatine phosphokinase increased 105.65 46.04 43 3708 33980 90590716
Alanine aminotransferase increased 95.64 46.04 60 3691 118278 90506418
Aspartate aminotransferase increased 82.66 46.04 52 3699 102885 90521811
Leukopenia 73.72 46.04 48 3703 100662 90524034
Neutrophil count decreased 69.91 46.04 41 3710 71491 90553205
Transaminases increased 66.76 46.04 32 3719 37160 90587536
Acute myeloid leukaemia 63.75 46.04 26 3725 20614 90604082
Disease progression 60.95 46.04 51 3700 156564 90468132
Capillary leak syndrome 58.27 46.04 15 3736 2752 90621944
Platelet count decreased 49.98 46.04 43 3708 136926 90487770
Asthenia 48.12 46.04 82 3669 533669 90091027
Nausea 47.91 46.04 126 3625 1110190 89514506
Extravasation 47.77 46.04 13 3738 2951 90621745
Hepatotoxicity 46.68 46.04 27 3724 45815 90578881

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 130.93 41.65 38 1731 10947 42608619
Rhabdomyolysis 96.28 41.65 52 1717 77967 42541599
Pancytopenia 71.74 41.65 50 1719 117693 42501873
Thrombocytopenia 64.25 41.65 57 1712 190222 42429344
Hepatotoxicity 62.05 41.65 27 1742 25140 42594426
Disease progression 54.41 41.65 46 1723 143610 42475956
Alanine aminotransferase increased 52.49 41.65 37 1732 88369 42531197
Neutropenia 52.39 41.65 52 1717 199379 42420187
Aspartate aminotransferase increased 49.79 41.65 34 1735 77129 42542437
Transaminases increased 46.32 41.65 24 1745 32861 42586705
Neutrophil count decreased 43.42 41.65 29 1740 63386 42556180

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
Neutropenia 237.55 42.08 168 4805 374452 110209874
Pancytopenia 224.68 42.08 131 4842 209482 110374844
Thrombocytopenia 183.68 42.08 140 4833 348745 110235581
Rhabdomyolysis 183.39 42.08 95 4878 120306 110464020
Anaemia 162.26 42.08 158 4815 546928 110037398
Febrile neutropenia 159.79 42.08 124 4849 316643 110267683
Haematotoxicity 153.45 42.08 51 4922 21031 110563295
Disease progression 121.73 42.08 95 4878 243939 110340387
Alanine aminotransferase increased 114.99 42.08 82 4891 183691 110400635
Aspartate aminotransferase increased 101.48 42.08 72 4901 159864 110424462
Neutrophil count decreased 99.57 42.08 64 4909 120877 110463449
Transaminases increased 99.19 42.08 51 4922 63339 110520987
Leukopenia 92.12 42.08 66 4907 148725 110435601
Hepatotoxicity 84.96 42.08 46 4927 63354 110520972
Blood creatine phosphokinase increased 73.61 42.08 44 4929 73033 110511293
Platelet count decreased 70.63 42.08 68 4905 230375 110353951
Hepatic function abnormal 63.12 42.08 43 4930 89252 110495074
Capillary leak syndrome 57.10 42.08 17 4956 4891 110579435
Acute myeloid leukaemia 54.82 42.08 29 4944 38081 110546245
Hypertransaminasaemia 54.45 42.08 25 4948 24230 110560096
Extravasation 48.72 42.08 15 4958 4830 110579496
White blood cell count decreased 45.90 42.08 54 4919 229336 110354990
Device related infection 42.93 42.08 25 4948 39494 110544832

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
CHEBI has role CHEBI:22333 alkylating agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50926 angiogenesis modulating agent
CHEBI has role CHEBI:67079 anti-inflammatory agent
CHEBI has role CHEBI:76507 marine metabolite

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)

None

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
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 30 sections
YONDELIS HUMAN PRESCRIPTION DRUG LABEL 1 59676-610 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 0.05 mg INTRAVENOUS NDA 30 sections
EVDI HUMAN PRESCRIPTION DRUG LABEL 1 60505-6423 INJECTION, SOLUTION, CONCENTRATE 0.05 mg INTRAVENOUS NDA 29 sections