Trabectedin
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Also known as Ecteinascidin 743Ecteinascidins trabectedinET-743Et743NSC-648766TrabectedinaTrabectedineYondelisSID144206315SID144206787
Summary
Trabectedin (CHEMBL450449) is an approved small-molecule antineoplastic agent (ATC L01CX01) targeting NR1I2; indicated across 28 conditions including liposarcoma and leiomyosarcoma; with CIViC clinical evidence for 6 variant-indication associations (e.g. EWSR1::FLI1 Fusion OR EWSR1::WT1 Fusion OR EWSR1::ATF1 Fusion in sarcoma).
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: L01CX01
- Targets: 1 (NR1I2)
- Indications: 28 conditions
- Clinical trials: 85
- Precision-oncology evidence (CIViC): 6 variant–indication associations
- Chemistry: 761.8 Da · C39H43N3O11S
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL450449 |
| Name | Trabectedin |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 108150 |
| ChEBI | CHEBI:84050 |
| ATC | L01CX01 |
| Molecular formula | C39H43N3O11S |
| Molecular weight | 761.8 |
| InChIKey | PKVRCIRHQMSYJX-AIFWHQITSA-N |
SMILES: CC1=CC2=C([C@@H]3[C@@H]4[C@H]5C6=C(C(=C7C(=C6[C@@H](N4[C@H]([C@H](C2)N3C)O)COC(=O)[C@@]8(CS5)C9=CC(=C(C=C9CCN8)O)OC)OCO7)C)OC(=O)C)C(=C1OC)O
IUPAC name: [(1R,2R,3R,11S,12S,14R,26R)-5,6’,12-trihydroxy-6,7’-dimethoxy-7,21,30-trimethyl-27-oxospiro[17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.13,11.02,13.04,9.015,23.016,20]triaconta-4(9),5,7,15,20,22-hexaene-26,1’-3,4-dihydro-2H-isoquinoline]-22-yl] acetate
ChEBI definition: A tetrahydroisoquinoline alkaloid obtained from a Caribbean tunicate Ecteinascidia turbinata. Used for the treatment of soft tissue sarcoma and relapsed ovarian cancer.
Pharmacological roles (ChEBI): antineoplastic agent, anti-inflammatory agent, angiogenesis modulating agent, alkylating agent.
Other ChEBI roles (chemical / environmental): marine metabolite.
Also known as: Ecteinascidin 743, Ecteinascidins trabectedin, ET-743, Et743, NSC-648766, Trabectedin, Trabectedina, Trabectedine, Yondelis, ecteinascidin 743, yondelis, TRABECTEDIN
Patent coverage: 499 distinct patent families (865 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 538 (62%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| NR1I2 | Pregnane X receptor | Antagonist | 8.52 | 0.3% | O75469 |
Bioactivity
No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).
Target pathways
Aggregated over 1 target gene(s): NR1I2.
Top Reactome pathways
2 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Nuclear Receptor transcription pathway | 1 | NR1I2 |
| SUMOylation of intracellular receptors | 1 | NR1I2 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| negative regulation of transcription by RNA polymerase II | 1 |
| regulation of DNA-templated transcription | 1 |
| xenobiotic metabolic process | 1 |
| signal transduction | 1 |
| steroid metabolic process | 1 |
| gene expression | 1 |
| positive regulation of gene expression | 1 |
| cell differentiation | 1 |
| intracellular receptor signaling pathway | 1 |
| xenobiotic catabolic process | 1 |
| xenobiotic transport | 1 |
| negative regulation of DNA-templated transcription | 1 |
| positive regulation of DNA-templated transcription | 1 |
| positive regulation of transcription by RNA polymerase II | 1 |
| intestinal epithelial structure maintenance | 1 |
Indications & clinical
Indications
28 indications (10 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| liposarcoma | 4 | MONDO:0005060 | EFO:0000569 |
| leiomyosarcoma | 4 | MONDO:0005058 | EFO:0000564 |
| neoplasm | 4 | MONDO:0005070 | EFO:0000616 |
| sarcoma | 4 | MONDO:0005089 | EFO:0000691 |
| ovarian carcinoma | 4 | MONDO:0005140 | EFO:0001075 |
| ovarian neoplasm | 4 | MONDO:0021068 | EFO:0003893 |
| soft tissue sarcoma | 4 | MONDO:0018078 | EFO:1001968 |
| ovarian cancer | 4 | MONDO:0008170 | MONDO:0008170 |
| dedifferentiated liposarcoma | 4 | MONDO:0020563 | EFO:0003085 |
| mesothelioma | 2 | MONDO:0005065 | EFO:0000588 |
| myxoid liposarcoma | 2 | MONDO:0013280 | EFO:0000613 |
| malignant pleural mesothelioma | 2 | MONDO:0005112 | EFO:0000770 |
| exocrine pancreatic carcinoma | 2 | MONDO:0005192 | EFO:0002618 |
| breast neoplasm | 2 | MONDO:0021100 | EFO:0003869 |
| soft tissue neoplasm | 2 | MONDO:0006424 | EFO:1000541 |
| hereditary breast ovarian cancer syndrome | 2 | MONDO:0003582 | Orphanet:145 |
| mesenchymal chondrosarcoma | 2 | MONDO:0006853 | EFO:1001041 |
| peritoneal neoplasm | 2 | MONDO:0006901 | MONDO:0002087 |
| fallopian tube neoplasm | 2 | MONDO:0021092 | MONDO:0002158 |
| endocrine gland neoplasm | 2 | MONDO:0002082 | EFO:0003769 |
| meningioma | 2 | MONDO:0016642 | MONDO:0016642 |
| reproductive system disorder | 2 | MONDO:0005039 | EFO:0000512 |
| B-cell chronic lymphocytic leukemia | 1 | MONDO:0004948 | EFO:0000095 |
| Ewing sarcoma | 1 | MONDO:0012817 | EFO:0000174 |
| lymphoid leukemia | 1 | MONDO:0005402 | EFO:0004289 |
3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 85.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 41 |
| PHASE3 | 16 |
| PHASE1 | 12 |
| Not specified | 10 |
| PHASE1/PHASE2 | 4 |
| PHASE2/PHASE3 | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05432791 | PHASE2/PHASE3 | ACTIVE_NOT_RECRUITING | Testing Olaparib and Temozolomide Versus the Usual Treatment for Uterine Leiomyosarcoma After Chemotherapy Has Stopped Working |
| NCT05597917 | PHASE3 | RECRUITING | tTF-NGR Randomized Study - STS |
| NCT06263231 | PHASE3 | ACTIVE_NOT_RECRUITING | A Study to Investigate Efficacy & Safety of Intratumoral INT230-6 Compared to US Standard of Care in Adults With Soft Tissue Sarcomas (INVINCIBLE-3) |
| NCT00113607 | PHASE3 | COMPLETED | An Efficacy and Safety Study for Yondelis (Trabectedin) in Patients With Advanced Relapsed Ovarian Cancer |
| NCT00796120 | PHASE3 | COMPLETED | An Efficacy and Safety Study of Trabectedin Versus Doxorubicin-Based Chemotherapy in Participants With Translocation-Related Sarcomas (TRS) |
| NCT01189253 | PHASE2/PHASE3 | TERMINATED | Doxorubicin Hydrochloride or Trabectedin in Treating Patients With Previously Untreated Advanced or Metastatic Soft Tissue Sarcoma |
| NCT01343277 | PHASE3 | COMPLETED | A Study of Trabectedin or Dacarbazine for the Treatment of Patients With Advanced Liposarcoma or Leiomyosarcoma |
| NCT01379989 | PHASE3 | COMPLETED | INOVATYON STUDY -International, Randomized Study in Patients With Ovarian Cancer |
| NCT01692678 | PHASE3 | COMPLETED | A Study of Trabectedin (YONDELIS) in Patients With Locally Advanced or Metastatic Liposarcoma or Leiomyosarcoma |
| NCT01710176 | PHASE3 | COMPLETED | Localized High-Risk Soft Tissue Sarcomas Of The Extremities And Trunk Wall In Adults: An Integrating Approach Comprising Standard Vs Histotype-Tailored Neoadjuvant Chemotherapy |
| NCT01846611 | PHASE3 | COMPLETED | A Study Comparing the Combination of Trabectedin (YONDELIS) and DOXIL/CAELYX With DOXIL/CAELYX for the Treatment of Advanced-Relapsed Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer |
| NCT02672527 | PHASE3 | COMPLETED | Trial Comparing Trabectedin to the Best Supportive Care in Patients With Sarcoma |
| NCT02903004 | PHASE3 | COMPLETED | Trial on Trabectedin (ET-743) vs Clinician’s Choice Chemotherapy in Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancers of BRCA Mutated or BRCAness Phenotype Patients |
| NCT02929394 | PHASE3 | TERMINATED | Trabectedin Maintenance Post 1st-line in STS |
| NCT02997358 | PHASE3 | COMPLETED | Study Comparing Efficacy of Doxorubicin With Trabectedin Followed by Trabectedin Versus Doxorubicine in Patients With Leiomyosarcoma |
| NCT03690739 | PHASE3 | TERMINATED | Evaluation of Symptom Benefit Rate of Trabectedin/PLD in Patients With Recurrent Ovarian Cancer |
| NCT03773510 | PHASE3 | WITHDRAWN | Study on Leiomyosarcoma, Liposarcomas and Synovial Sarcoma With Trabectedin |
| NCT04979442 | PHASE3 | TERMINATED | Treatment of Milademetan Versus Trabectedin in Patient With Dedifferentiated Liposarcoma |
| NCT02275286 | PHASE1/PHASE2 | RECRUITING | Trabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients |
| NCT03138161 | PHASE1/PHASE2 | RECRUITING | SAINT:Trabectedin, Ipilimumab and Nivolumab for Previously Treated Advanced Soft Tissue Sarcoma |
| NCT03886311 | PHASE2 | RECRUITING | Talimogene Laherparepvec, Nivolumab and Trabectedin for Sarcoma |
| NCT04305548 | PHASE2 | RECRUITING | Study on Trabectedin in Advanced Rearranged Mesenchymal Chondrosarcoma |
| NCT04383119 | PHASE2 | RECRUITING | Trial in Patients With Metastatic or Locally Advanced Leiomyosarcoma |
| NCT04535271 | PHASE2 | RECRUITING | Metronomic Trabectedin, Gemcitabine, and Dacarbazine for Soft Tissue Sarcoma |
| NCT06524583 | PHASE2 | RECRUITING | Interest of Post-operative Chemotherapy in Patients With Localised Uterine Leiomyosarcoma Suspected of Having a High Risk of Recurrence Based on a Biological Test Performed on the Tumour |
| NCT07076186 | PHASE2 | RECRUITING | Phase II Decentralized Pragmatic Trial of Adjuvant Doxorubicin - Trabectedin Chemotherapy in uLMS |
| NCT00003939 | PHASE2 | COMPLETED | Ecteinascidin 743 in Treating Patients With Advanced Soft Tissue Sarcoma |
| NCT00005625 | PHASE2 | COMPLETED | Ecteinascidin 743 in Treating Patients With Previously Treated Metastatic Osteosarcoma |
| NCT00017030 | PHASE2 | COMPLETED | Ecteinascidin 743 in Treating Patients With Unresectable Advanced or Metastatic Soft Tissue Sarcoma |
| NCT00027508 | PHASE2 | TERMINATED | Ecteinascidin 743 in Treating Patients With Malignant Mesothelioma |
| NCT00050414 | PHASE2 | COMPLETED | A Study of Trabectedin in Patients With Advanced Ovarian Cancer |
| NCT00050427 | PHASE2 | COMPLETED | A Study of ET-743 (Trabectedin) in Patients With Advanced Breast Cancer |
| NCT00050440 | PHASE2 | COMPLETED | Phase 2 Study of ET-743 (Trabectedin) in Patients With Persistent or Recurrent Endometrial Carcinoma |
| NCT00060944 | PHASE2 | COMPLETED | A Study to Assess Treatment With 2 Different Dosing Schedules of Trabectidin Administered to Patients With Advanced Cancer |
| NCT00070109 | PHASE2 | COMPLETED | Trabectedin in Treating Young Patients With Recurrent or Refractory Soft Tissue Sarcoma or Ewing’s Family of Tumors |
| NCT00072670 | PHASE2 | COMPLETED | A Phase 2 Study of Trabectedin (Yondelis) in Adult Male Participants With Advanced Prostate Cancer |
| NCT00379145 | PHASE2 | COMPLETED | Trabectedin in Treating Patients With Advanced, Persistent, or Recurrent Leiomyosarcoma of the Uterus |
| NCT00569673 | PHASE2 | COMPLETED | Docetaxel, Trabectedin, and G-CSF or Pegfilgrastim in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer |
| NCT00579501 | PHASE2 | COMPLETED | Safety and Efficacy Study of Trabectedin for the Treatment of Localized Myxoid / Round Cell Liposarcoma |
| NCT00580112 | PHASE2 | COMPLETED | An Efficacy Study of Trabectedin in the Treatment of Participants With Specific Subtypes of Metastatic Breast Cancer |
Clinical evidence (CIViC)
Variant × indication × effect (6 predictive associations from 6 curated evidence items):
| Variant | Indication | Effect | Therapy | Level | CIViC |
|---|---|---|---|---|---|
| EWSR1::FLI1 Fusion OR EWSR1::WT1 Fusion OR EWSR1::ATF1 Fusion | Sarcoma | Sensitivity/Response | Trabectedin | CIViC B | EID12544 |
| EWSR1::ATF1 Fusion | Clear Cell Sarcoma | Sensitivity/Response | Trabectedin | CIViC C | EID12166 |
| EWSR1::NR4A3 Fusion OR TAF15::NR4A3 Fusion | Extraskeletal Myxoid Chondrosarcoma | Sensitivity/Response | Trabectedin | CIViC C | EID12545 |
| HEY1::NCOA2 Fusion | Mesenchymal Chondrosarcoma | Sensitivity/Response | Trabectedin | CIViC C | EID12585 |
| EWSR1::FLI1 Fusion | Cancer | Sensitivity/Response | Trabectedin | CIViC D | EID12543 |
| PARP1 OVEREXPRESSION | Sarcoma | Sensitivity/Response | Trabectedin + Olaparib | CIViC D | EID7868 |
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 5 variant annotation(s) for this drug (gene-keyed; see PharmGKB).
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
278 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| BOSENTAN | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| CRIZOTINIB | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| DACOMITINIB | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| DESOXYCORTICOSTERONE PIVALATE | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| FULVESTRANT | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| GEFITINIB | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| TADALAFIL | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| ABACAVIR | ChEMBL | Phase 4 (approved) | NR1I2 |
| ACENOCOUMAROL | ChEMBL | Phase 4 (approved) | NR1I2 |
| ACETAMINOPHEN | ChEMBL | Phase 4 (approved) | NR1I2 |
| ACITRETIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| ADAPALENE | ChEMBL | Phase 4 (approved) | NR1I2 |
| ALECTINIB | ChEMBL | Phase 4 (approved) | NR1I2 |
| ALPIDEM | ChEMBL | Phase 4 (approved) | NR1I2 |
| AMBRISENTAN | ChEMBL | Phase 4 (approved) | NR1I2 |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| AMSACRINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| ATAZANAVIR | ChEMBL | Phase 4 (approved) | NR1I2 |
| ATORVASTATIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| BEDAQUILINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | NR1I2 |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BENZTHIAZIDE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | NR1I2 |
| BETAMETHASONE DIPROPIONATE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BIFONAZOLE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BITHIONOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| BRIMONIDINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| BUCLIZINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BUTENAFINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BUTOCONAZOLE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CALCIPOTRIENE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CALCITRIOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | NR1I2 |
| CANNABIDIOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| CAPSAICIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFACLOR | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFAMANDOLE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFEPIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFMENOXIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFOTAXIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFOXITIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFPODOXIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFTAZIDIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFTIZOXIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFTRIAXONE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFUROXIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEPHALORIDINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEPHALOTHIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEPHAPIRIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEPHRADINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CHLOROXINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CHLORPROTHIXENE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CICLESONIDE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CICLOPIROX | ChEMBL | Phase 4 (approved) | NR1I2 |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CLOBETASOL PROPIONATE | ChEMBL | Phase 4 (approved) | NR1I2 |
Related Atlas pages
- Genes: NR1I2
- Diseases: liposarcoma, leiomyosarcoma, neoplasm, sarcoma, ovarian carcinoma, ovarian neoplasm, soft tissue sarcoma, ovarian cancer, dedifferentiated liposarcoma, clear cell sarcoma, extraskeletal myxoid chondrosarcoma, pediatric mesenchymal chondrosarcoma, cancer
- Drugs: Bosentan, Crizotinib, Dacomitinib, Desoxycorticosterone Pivalate, Fulvestrant, Gefitinib, Tadalafil, Abacavir, Acenocoumarol, Acetaminophen, Acitretin, Adapalene, Alectinib, Alpidem, Ambrisentan, Amlodipine, Amsacrine, Atazanavir, Atorvastatin, Bedaquiline, Benfluorex, Benzbromarone, Benzthiazide, Bepridil, Betamethasone Dipropionate, Bifonazole, Bithionol, Brimonidine, Bromperidol, Buclizine, Butenafine, Butoconazole, Calcipotriene, Calcitriol, Candesartan Cilexetil, Cannabidiol, Capsaicin, Carvedilol, Cefaclor, Cefamandole, Cefepime, Cefmenoxime, Cefotaxime, Cefoxitin, Cefpodoxime, Ceftazidime, Ceftizoxime, Ceftriaxone, Cefuroxime, Cephaloridine, Cephalothin, Cephapirin, Cephradine, Chlorhexidine, Chloroxine, Chlorprothixene, Ciclesonide, Ciclopirox, Clemastine, Clobetasol Propionate