Identification

Name
Trabectedin
Accession Number
DB05109
Type
Small Molecule
Groups
Approved, Investigational
Description

Trabectedin, also referred as ET-743 during its development, is a marine derived antitumoral agent discovered in the Carribean tunicate Ecteinascidia turbinata and now produced synthetically. Trabectedin has a unique mechanism of action. It binds to the minor groove of DNA interfering with cell division and genetic transcription processes and DNA repair machinery.It is approved for use in Europe, Russia and South Korea for the treatment of advanced soft tissue sarcoma. It is also undergoing clinical trials for the treatment of breast, prostate, and paediatric sarcomas. The European Commission and the U.S. Food and Drug Administration (FDA) have granted orphan drug status to trabectedin for soft tissue sarcomas and ovarian cancer. On October 23, 2015, the FDA approved trabectedin, (as Yondelis), for the treatment of specific soft tissue sarcomas.

Structure
Thumb
Synonyms
  • Ecteinascidin 743
External IDs
ET-743 / NSC 684766 / NSC-648766
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
YondelisPowder, for solution1 mgIntravenousJanssen Pharmaceuticals2010-08-05Not applicableCanada
YondelisInjection, powder, lyophilized, for solution.05 mg/mLIntravenousJanssen, Lp2015-10-23Not applicableUs
Categories
UNII
ID0YZQ2TCP
CAS number
114899-77-3
Weight
Average: 761.837
Monoisotopic: 761.261829923
Chemical Formula
C39H43N3O11S
InChI Key
PKVRCIRHQMSYJX-AIFWHQITSA-N
InChI
InChI=1S/C39H43N3O11S/c1-16-9-20-10-22-37(46)42-23-13-50-38(47)39(21-12-25(48-5)24(44)11-19(21)7-8-40-39)14-54-36(30(42)29(41(22)4)26(20)31(45)32(16)49-6)28-27(23)35-34(51-15-52-35)17(2)33(28)53-18(3)43/h9,11-12,22-23,29-30,36-37,40,44-46H,7-8,10,13-15H2,1-6H3/t22-,23-,29+,30+,36+,37-,39+/m0/s1
IUPAC Name
(1R,2R,3R,11S,12S,14R,26R)-5,6',12-trihydroxy-6,7'-dimethoxy-7,21,30-trimethyl-27-oxo-3',4'-dihydro-2'H-17,19,28-trioxa-24-thia-13,30-diazaspiro[heptacyclo[12.9.6.1³,¹¹.0²,¹³.0⁴,⁹.0¹⁵,²³.0¹⁶,²⁰]triacontane-26,1'-isoquinoline]-4,6,8,15,20,22-hexaen-22-yl acetate
SMILES
[H][[email protected]@]12[[email protected]@H]3SC[[email protected]]4(NCCC5=C4C=C(OC)C(O)=C5)C(=O)OC[[email protected]](N1[[email protected]@H](O)[[email protected]@H]1CC4=CC(C)=C(OC)C(O)=C4[[email protected]]2N1C)C1=C2OCOC2=C(C)C(OC(C)=O)=C31

Pharmacology

Indication

Indicated for treatment of advanced soft tissue sarcoma in patients refractory to or unsuitable to receive anthracycline or ifosfamide chemotherapy in Europe, Russia and South Korea. Approved for orphan drug status by the U.S. FDA for treatment of soft tissue sarcomas and ovarian cancer. Investigated for use/treatment in cancer/tumors (unspecified), gastric cancer, ovarian cancer, pediatric indications, sarcoma, and solid tumors.

Structured Indications
Pharmacodynamics

Two of the rings in the drug's structure allows it to covalently bind to the minor groove of DNA. The third ring protrudes from the DNA which lets it interact with nearby nuclear proteins. This has the additive effect of blocking cell division at the G2 phase.

Mechanism of action

Trabectedin interacts with the minor groove of DNA and alkylates guanine at the N2 position, which bends towards the major groove. In this manner, it is thought that the drug affects various transcription factors involved in cell proliferation, particularly via the transcription-coupled nucleotide excision repair system. Trabectedin blocks the cell cycle at the G2 phase, while cells at the G1 phase are most sensitive to the drug. It also inhibits overexpression of the multidrug resistance-1 gene (MDR-1) coding for the P-glycoprotein that is a major factor responsible for cells developing resistance to cancer drugs. The agent is also thought to interfere with the nucleotide excision repair pathways of cancer cells, suggesting that it could be effective in the treatment of many cancer types including melanoma and sarcoma, as well as lung, breast, ovarian, endometrial and prostate cancers; clinical evaluations are underway in these indications.

TargetActionsOrganism
ADNA
binder
Human
Absorption

Administered intravenously.

Volume of distribution
Not Available
Protein binding

94 to 98%

Metabolism
Route of elimination
Not Available
Half life

33-50 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Trabectedin can be increased when it is combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Trabectedin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Trabectedin.Experimental
AmiodaroneThe serum concentration of Trabectedin can be increased when it is combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Trabectedin can be increased when it is combined with Aprepitant.Approved, Investigational
ArmodafinilThe metabolism of Trabectedin can be decreased when combined with Armodafinil.Approved, Investigational
ArtemetherThe metabolism of Trabectedin can be decreased when combined with Artemether.Approved
AtazanavirThe serum concentration of Trabectedin can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe serum concentration of Trabectedin can be increased when it is combined with Atomoxetine.Approved
AtorvastatinAtorvastatin may increase the myopathic rhabdomyolysis activities of Trabectedin.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Trabectedin.Investigational
BetaxololThe metabolism of Trabectedin can be decreased when combined with Betaxolol.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Trabectedin.Approved, Investigational
BoceprevirThe serum concentration of Trabectedin can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe serum concentration of Trabectedin can be increased when it is combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Trabectedin can be decreased when it is combined with Bosentan.Approved, Investigational
BupropionThe metabolism of Trabectedin can be decreased when combined with Bupropion.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Trabectedin.Approved
CapecitabineThe metabolism of Trabectedin can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe serum concentration of Trabectedin can be decreased when it is combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Trabectedin can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Trabectedin can be increased when it is combined with Ceritinib.Approved
CerivastatinCerivastatin may increase the myopathic rhabdomyolysis activities of Trabectedin.Withdrawn
ChloramphenicolThe metabolism of Trabectedin can be decreased when combined with Chloramphenicol.Approved, Vet Approved
ChloroquineThe metabolism of Trabectedin can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Trabectedin can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Trabectedin can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Trabectedin can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Trabectedin can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Trabectedin can be decreased when combined with Citalopram.Approved
ClarithromycinThe serum concentration of Trabectedin can be increased when it is combined with Clarithromycin.Approved
ClemastineThe serum concentration of Trabectedin can be increased when it is combined with Clemastine.Approved
ClobazamThe metabolism of Trabectedin can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Trabectedin can be decreased when combined with Clomipramine.Approved, Vet Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Trabectedin.Approved
ClotrimazoleThe serum concentration of Trabectedin can be increased when it is combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Trabectedin is combined with Clozapine.Approved
CobicistatThe serum concentration of Trabectedin can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Trabectedin can be decreased when combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Trabectedin can be increased when it is combined with Conivaptan.Approved, Investigational
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Trabectedin.Approved
CrisaboroleThe metabolism of Trabectedin can be decreased when combined with Crisaborole.Approved
CrizotinibThe serum concentration of Trabectedin can be increased when it is combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Trabectedin.Approved, Investigational
CyclosporineThe serum concentration of Trabectedin can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Trabectedin.Experimental
Cyproterone acetateThe serum concentration of Trabectedin can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Trabectedin can be decreased when it is combined with Dabrafenib.Approved
DarifenacinThe metabolism of Trabectedin can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Trabectedin can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Trabectedin can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Trabectedin can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe serum concentration of Trabectedin can be increased when it is combined with Delavirdine.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Trabectedin.Approved
DesipramineThe metabolism of Trabectedin can be decreased when combined with Desipramine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Trabectedin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Trabectedin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Trabectedin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Trabectedin.Approved
DihydroergotamineThe serum concentration of Trabectedin can be increased when it is combined with Dihydroergotamine.Approved
DiltiazemThe serum concentration of Trabectedin can be increased when it is combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Trabectedin can be decreased when combined with Diphenhydramine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Trabectedin.Approved, Investigational
DosulepinThe metabolism of Trabectedin can be decreased when combined with Dosulepin.Approved
DoxycyclineThe serum concentration of Trabectedin can be increased when it is combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe serum concentration of Trabectedin can be increased when it is combined with Dronedarone.Approved
DuloxetineThe metabolism of Trabectedin can be decreased when combined with Duloxetine.Approved
EfavirenzThe metabolism of Trabectedin can be decreased when combined with Efavirenz.Approved, Investigational
EliglustatThe metabolism of Trabectedin can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Trabectedin can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe serum concentration of Trabectedin can be increased when it is combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe metabolism of Trabectedin can be decreased when combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Trabectedin can be decreased when combined with Esomeprazole.Approved, Investigational
EthanolEthanol may increase the hepatotoxic activities of Trabectedin.Approved
EtravirineThe metabolism of Trabectedin can be decreased when combined with Etravirine.Approved
FingolimodTrabectedin may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FloxuridineThe metabolism of Trabectedin can be decreased when combined with Floxuridine.Approved
FluconazoleThe serum concentration of Trabectedin can be increased when it is combined with Fluconazole.Approved
FluorouracilThe metabolism of Trabectedin can be decreased when combined with Fluorouracil.Approved
FluoxetineThe metabolism of Trabectedin can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvastatinFluvastatin may increase the myopathic rhabdomyolysis activities of Trabectedin.Approved
FluvoxamineThe serum concentration of Trabectedin can be increased when it is combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe serum concentration of Trabectedin can be increased when it is combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Trabectedin can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Trabectedin can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Trabectedin can be increased when it is combined with Fusidic Acid.Approved
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Trabectedin.Investigational
GemfibrozilThe metabolism of Trabectedin can be decreased when combined with Gemfibrozil.Approved
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Trabectedin.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Trabectedin.Experimental
HaloperidolThe metabolism of Trabectedin can be decreased when combined with Haloperidol.Approved
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Trabectedin.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Trabectedin.Approved, Withdrawn
IdelalisibThe serum concentration of Trabectedin can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Trabectedin can be increased when it is combined with Imatinib.Approved
ImipramineThe metabolism of Trabectedin can be decreased when combined with Imipramine.Approved
IndinavirThe serum concentration of Trabectedin can be increased when it is combined with Indinavir.Approved
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Trabectedin.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Trabectedin.Investigational
IrbesartanThe metabolism of Trabectedin can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe serum concentration of Trabectedin can be increased when it is combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Trabectedin can be decreased when combined with Isoniazid.Approved
IsradipineThe serum concentration of Trabectedin can be increased when it is combined with Isradipine.Approved
ItraconazoleThe serum concentration of Trabectedin can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Trabectedin can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe serum concentration of Trabectedin can be increased when it is combined with Ketoconazole.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Trabectedin.Experimental
LeflunomideThe risk or severity of adverse effects can be increased when Trabectedin is combined with Leflunomide.Approved, Investigational
LobeglitazoneThe metabolism of Trabectedin can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe serum concentration of Trabectedin can be increased when it is combined with Lopinavir.Approved
LorcaserinThe metabolism of Trabectedin can be decreased when combined with Lorcaserin.Approved
LosartanThe metabolism of Trabectedin can be decreased when combined with Losartan.Approved
LovastatinLovastatin may increase the myopathic rhabdomyolysis activities of Trabectedin.Approved, Investigational
LuliconazoleThe serum concentration of Trabectedin can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Trabectedin can be decreased when it is combined with Lumacaftor.Approved
LumefantrineThe metabolism of Trabectedin can be decreased when combined with Lumefantrine.Approved
ManidipineThe metabolism of Trabectedin can be decreased when combined with Manidipine.Approved, Investigational
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Trabectedin.Investigational, Withdrawn
MethadoneThe metabolism of Trabectedin can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Trabectedin can be decreased when combined with Methotrimeprazine.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Trabectedin.Experimental
MetoprololThe metabolism of Trabectedin can be decreased when combined with Metoprolol.Approved, Investigational
MevastatinMevastatin may increase the myopathic rhabdomyolysis activities of Trabectedin.Experimental
MidostaurinThe metabolism of Trabectedin can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Trabectedin can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe metabolism of Trabectedin can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Trabectedin can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Trabectedin can be decreased when combined with Moclobemide.Approved
ModafinilThe metabolism of Trabectedin can be decreased when combined with Modafinil.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Trabectedin is combined with Natalizumab.Approved, Investigational
NefazodoneThe serum concentration of Trabectedin can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Trabectedin can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Trabectedin can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Trabectedin can be decreased when it is combined with Nevirapine.Approved
NicardipineThe metabolism of Trabectedin can be decreased when combined with Nicardipine.Approved
NicotineThe metabolism of Trabectedin can be decreased when combined with Nicotine.Approved
NilotinibThe serum concentration of Trabectedin can be increased when it is combined with Nilotinib.Approved, Investigational
OlaparibThe serum concentration of Trabectedin can be increased when it is combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Trabectedin.Experimental, Investigational
OmeprazoleThe metabolism of Trabectedin can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Trabectedin can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Trabectedin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Trabectedin.Approved, Vet Approved
PalbociclibThe serum concentration of Trabectedin can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Trabectedin can be increased when it is combined with Panobinostat.Approved, Investigational
PantoprazoleThe metabolism of Trabectedin can be decreased when combined with Pantoprazole.Approved
ParoxetineThe metabolism of Trabectedin can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Trabectedin can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe serum concentration of Trabectedin can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Trabectedin.Experimental
PhenobarbitalThe serum concentration of Trabectedin can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Trabectedin can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Trabectedin.Approved, Investigational
PitavastatinPitavastatin may increase the myopathic rhabdomyolysis activities of Trabectedin.Approved
PosaconazoleThe serum concentration of Trabectedin can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinPravastatin may increase the myopathic rhabdomyolysis activities of Trabectedin.Approved
PrimidoneThe serum concentration of Trabectedin can be decreased when it is combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Trabectedin can be decreased when combined with Promazine.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Trabectedin.Experimental
PyrimethamineThe metabolism of Trabectedin can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuinidineThe metabolism of Trabectedin can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Trabectedin can be decreased when combined with Quinine.Approved
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Trabectedin is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Trabectedin.Approved
RanolazineThe serum concentration of Trabectedin can be increased when it is combined with Ranolazine.Approved, Investigational
RifabutinThe serum concentration of Trabectedin can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Trabectedin can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Trabectedin can be decreased when it is combined with Rifapentine.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Trabectedin.Investigational
RitonavirThe metabolism of Trabectedin can be decreased when combined with Ritonavir.Approved, Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Trabectedin.Approved
RolapitantThe metabolism of Trabectedin can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Trabectedin can be decreased when combined with Ropinirole.Approved, Investigational
RosuvastatinRosuvastatin may increase the myopathic rhabdomyolysis activities of Trabectedin.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Trabectedin.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Trabectedin.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Trabectedin.Approved
SaquinavirThe serum concentration of Trabectedin can be increased when it is combined with Saquinavir.Approved, Investigational
SecobarbitalThe metabolism of Trabectedin can be increased when combined with Secobarbital.Approved, Vet Approved
SertralineThe metabolism of Trabectedin can be decreased when combined with Sertraline.Approved
SildenafilThe serum concentration of Trabectedin can be increased when it is combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Trabectedin can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Trabectedin can be increased when it is combined with Simeprevir.Approved
SimvastatinSimvastatin may increase the myopathic rhabdomyolysis activities of Trabectedin.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Trabectedin.Approved
SorafenibThe metabolism of Trabectedin can be decreased when combined with Sorafenib.Approved, Investigational
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Trabectedin.Investigational
St. John's WortThe serum concentration of Trabectedin can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Trabectedin can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe metabolism of Trabectedin can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Trabectedin can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe serum concentration of Trabectedin can be increased when it is combined with Sulfisoxazole.Approved, Vet Approved
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Trabectedin.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Trabectedin.Investigational
TelaprevirThe serum concentration of Trabectedin can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Trabectedin can be increased when it is combined with Telithromycin.Approved
TerbinafineThe metabolism of Trabectedin can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Trabectedin.Investigational
ThioridazineThe metabolism of Trabectedin can be decreased when combined with Thioridazine.Approved, Withdrawn
TicagrelorThe metabolism of Trabectedin can be decreased when combined with Ticagrelor.Approved
TiclopidineThe serum concentration of Trabectedin can be increased when it is combined with Ticlopidine.Approved
TipranavirThe metabolism of Trabectedin can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Trabectedin can be decreased when it is combined with Tocilizumab.Approved
TofacitinibTrabectedin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TolbutamideThe metabolism of Trabectedin can be decreased when combined with Tolbutamide.Approved
TopiramateThe metabolism of Trabectedin can be decreased when combined with Topiramate.Approved
TopiroxostatThe metabolism of Trabectedin can be decreased when combined with Topiroxostat.Approved, Investigational
TranylcypromineThe metabolism of Trabectedin can be decreased when combined with Tranylcypromine.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Trabectedin.Approved, Investigational
TrimethoprimThe metabolism of Trabectedin can be decreased when combined with Trimethoprim.Approved, Vet Approved
UbidecarenoneUbidecarenone may increase the myopathic rhabdomyolysis activities of Trabectedin.Approved, Experimental
Valproic AcidThe metabolism of Trabectedin can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Trabectedin can be decreased when combined with Valsartan.Approved, Investigational
VenlafaxineThe serum concentration of Trabectedin can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Trabectedin can be increased when it is combined with Verapamil.Approved
VoriconazoleThe serum concentration of Trabectedin can be increased when it is combined with Voriconazole.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Trabectedin.Approved
ZafirlukastThe metabolism of Trabectedin can be decreased when combined with Zafirlukast.Approved, Investigational
ZiprasidoneThe serum concentration of Trabectedin can be increased when it is combined with Ziprasidone.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Trabectedin.Approved
ZucapsaicinThe metabolism of Trabectedin can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

Synthesis Reference

Elias J. Corey, David Gin, "Process for producing ecteinascidin compounds." U.S. Patent US5721362, issued December, 1995.

US5721362
General References
  1. Tavecchio M, Natoli C, Ubezio P, Erba E, D'Incalci M: Dynamics of cell cycle phase perturbations by trabectedin (ET-743) in nucleotide excision repair (NER)-deficient and NER-proficient cells, unravelled by a novel mathematical simulation approach. Cell Prolif. 2007 Dec;40(6):885-904. [PubMed:18021177]
  2. Krasner CN, McMeekin DS, Chan S, Braly PS, Renshaw FG, Kaye S, Provencher DM, Campos S, Gore ME: A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. Br J Cancer. 2007 Dec 17;97(12):1618-24. Epub 2007 Nov 13. [PubMed:18000504]
  3. Carter NJ, Keam SJ: Trabectedin : a review of its use in the management of soft tissue sarcoma and ovarian cancer. Drugs. 2007;67(15):2257-76. [PubMed:17927287]
  4. Authors unspecified: Trabectedin: Ecteinascidin 743, Ecteinascidin-743, ET 743, ET-743, NSC 684766. Drugs R D. 2006;7(5):317-28. [PubMed:16922593]
  5. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
External Links
Human Metabolome Database
HMDB15609
PubChem Compound
108150
PubChem Substance
99443229
ChemSpider
97236
ChEBI
84050
ChEMBL
CHEMBL450449
PharmGKB
PA165958349
HET
ECT
Wikipedia
Trabectedin
ATC Codes
L01CX01 — Trabectedin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (824 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentBone Tumors / Soft Tissue Sarcoma (STS)1
1CompletedTreatmentHepatic Insufficiency / Neoplasm Metastases1
1CompletedTreatmentLeiomyosarcomas / Liposarcoma1
1CompletedTreatmentNeoplasms / Neoplasms by Histologic Type / Neoplasms, Connective and Soft Tissue / Sarcomas / Soft Tissue Sarcoma (STS)1
1CompletedTreatmentTumors, Solid1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentUnspecified Childhood Solid Tumor, Protocol Specific1
1RecruitingBasic ScienceSoft Tissue Sarcoma Adult1
1, 2CompletedTreatmentNeoplasm Metastases1
1, 2RecruitingTreatmentAdvanced Soft Tissue Sarcoma / Metastatic Soft Tissue Sarcoma1
1, 2RecruitingTreatmentMetastatic Leiomyosarcoma / Metastatic Liposarcoma1
1, 2RecruitingTreatmentMyxoid Liposarcoma / Soft Tissue Sarcoma (STS)1
2Active Not RecruitingTreatmentLeiomyosarcomas1
2Active Not RecruitingTreatmentMetastatic and Locally Advanced Soft Tissue Tumor Patients Unfit to Receive / Standard Chemotherapy1
2Active Not RecruitingTreatmentRecurrent High Grade Meningioma1
2Active Not RecruitingTreatmentSoft Tissue Sarcoma (STS) / Uterine Sarcoma1
2CompletedTreatmentBrain and Central Nervous System Tumors / Cancer, Ovarian / Endometrial Cancers / Gastrointestinal Stromal Tumors / Sarcomas / Small Intestine Cancer1
2CompletedTreatmentCancer, Ovarian / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
2CompletedTreatmentDisease, Adnexal / Endocrine Gland Neoplasms / Genital Diseases, Female / Neoplasms / Neoplasms by Site / Neoplasms, Ovarian / Ovarian Diseases1
2CompletedTreatmentGenital Neoplasms, Female Urogenital Neoplasms / Neoplasms, Endometrial / Uterine Neoplasms1
2CompletedTreatmentLeiomyosarcomas / Liposarcoma1
2CompletedTreatmentMalignant Neoplasm of Pancreas1
2CompletedTreatmentMyxoid Liposarcoma1
2CompletedTreatmentNeoplasms, Breast1
2CompletedTreatmentPeripheral Primitive Neuroectodermal Tumor / Previously Treated Childhood Rhabdomyosarcoma / Recurrent Childhood Rhabdomyosarcoma / Recurrent Childhood Soft Tissue Sarcoma / Recurrent Ewing Sarcoma1
2CompletedTreatmentProstate Cancer2
2CompletedTreatmentSarcomas3
2CompletedTreatmentSoft Tissue Leiomyosarcoma / Uterus Leiomyosarcoma1
2CompletedTreatmentTumors, Solid1
2Not Yet RecruitingTreatmentCancers With DNA Repair-Deficiency1
2Not Yet RecruitingTreatmentCarcinosarcomas Uterine / Ovarian Carcinosarcoma1
2Not Yet RecruitingTreatmentSolitary Fibrous Tumors1
2RecruitingTreatmentLeiomyosarcomas / Liposarcoma1
2RecruitingTreatmentMalignant Pleural Mesothelioma (MPM)1
2RecruitingTreatmentOvarian Epithelial Cancer Recurrent1
2TerminatedTreatmentMesothelioma, Malignant1
2TerminatedTreatmentSarcomas1
2Unknown StatusTreatmentBRCA1 and BRCA2 Mutation Carrier and BRCAness Phenotype1
2, 3TerminatedTreatmentSarcomas1
3Active Not RecruitingTreatmentAdvanced or Metastatic Liposarcoma or Leiomyosarcoma1
3CompletedTreatmentAdvanced Liposarcoma or Leiomyosarcoma1
3CompletedTreatmentCancer, Ovarian1
3CompletedTreatmentSarcomas1
3Not Yet RecruitingTreatmentUterine or Soft Tissue Leiomyosarcoma1
3RecruitingTreatmentAbdominal wall neoplasm / Fallopian Tube Neoplasms / Neoplasms, Ovarian1
3RecruitingTreatmentCancer, Ovarian1
3RecruitingTreatmentNeoplasms, Ovarian1
3RecruitingTreatmentSoft Tissue Sarcoma (STS)2
Not AvailableActive Not RecruitingNot AvailableOvarian Epithelial Cancer Recurrent1
Not AvailableNo Longer AvailableNot AvailableSarcomas1
Not AvailableNo Longer AvailableNot AvailableSoft Tissue Sarcoma (STS)1
Not AvailableRecruitingNot AvailableRecurrent Ovarian Cancer1
Not AvailableRecruitingNot AvailableSoft Tissue Sarcoma (STS)2
Not AvailableRecruitingTreatmentSarcomas1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous.05 mg/mL
Powder, for solutionIntravenous1 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2428160No2009-10-132021-11-06Canada
CA2373794No2005-10-112020-05-15Canada
US8895557No2008-01-072028-01-07Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.328 mg/mLALOGPS
logP2.04ALOGPS
logP3.99ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)9.27ChemAxon
pKa (Strongest Basic)7.66ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area168.72 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity196.92 m3·mol-1ChemAxon
Polarizability77.72 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.5216
Blood Brain Barrier-0.9238
Caco-2 permeable-0.6788
P-glycoprotein substrateSubstrate0.8988
P-glycoprotein inhibitor INon-inhibitor0.6957
P-glycoprotein inhibitor IINon-inhibitor0.74
Renal organic cation transporterNon-inhibitor0.8321
CYP450 2C9 substrateNon-substrate0.8211
CYP450 2D6 substrateNon-substrate0.7689
CYP450 3A4 substrateSubstrate0.6512
CYP450 1A2 substrateNon-inhibitor0.804
CYP450 2C9 inhibitorNon-inhibitor0.5287
CYP450 2D6 inhibitorNon-inhibitor0.6514
CYP450 2C19 inhibitorNon-inhibitor0.5436
CYP450 3A4 inhibitorInhibitor0.8832
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6677
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.8734
BiodegradationNot ready biodegradable0.9782
Rat acute toxicity2.6136 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9942
hERG inhibition (predictor II)Inhibitor0.5329
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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 benzazocines. These are organic compounds containing the benzazocine ring system, which consists of a benzene ring bound to an azocine ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzazocines
Direct Parent
Benzazocines
Alternative Parents
Tetrahydroisoquinolines / Alpha amino acids and derivatives / Benzodioxoles / Anisoles / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Alkyl aryl ethers / N-methylpiperazines / Aralkylamines / Dicarboxylic acids and derivatives
show 14 more
Substituents
Benzazocine / Tetrahydroisoquinoline / Alpha-amino acid or derivatives / Benzodioxole / Anisole / Alkyl aryl ether / N-methylpiperazine / N-alkylpiperazine / Aralkylamine / 1-hydroxy-4-unsubstituted benzenoid
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, acetate ester, polyphenol, organic sulfide, bridged compound, isoquinoline alkaloid, hemiaminal, lactone, azaspiro compound, organic heteropolycyclic compound, oxaspiro compound (CHEBI:84050)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. D'Incalci M, Galmarini CM: A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther. 2010 Aug;9(8):2157-63. doi: 10.1158/1535-7163.MCT-10-0263. Epub 2010 Jul 20. [PubMed:20647340]
  3. Marco E, David-Cordonnier MH, Bailly C, Cuevas C, Gago F: Further insight into the DNA recognition mechanism of trabectedin from the differential affinity of its demethylated analogue ecteinascidin ET729 for the triplet DNA binding site CGA. J Med Chem. 2006 Nov 16;49(23):6925-9. [PubMed:17154523]

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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
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
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]

Drug created on October 21, 2007 16:23 / Updated on November 19, 2017 20:33