Trabectedin
[CAS# 114899-77-3]

Identification

• Classification: API >> Antibiotics
• Name: Trabectedin
• Synonyms: Ecteinascidin; Ecteinascidin 743; Ecteinascidine 743; Et 743; NSC 648766
• Molecular Formula: C₃₉H₄₃N₃O₁₁S
• Molecular Weight: 761.84
• CAS Registry Number: 114899-77-3
• EC Number: 695-026-8
• 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

Properties

• Solubility: Practically insoluble (0.055 g/L) (25 °C), Calc.^*
• Density: 1.55±0.1 g/cm³ (20 °C 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2013 ACD/Labs)

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS08 Danger
• Risk Statements: H300-H312-H332-H341-H361-H373
• Safety Statements: P203-P260-P261-P264-P270-P271-P280-P301+P316-P302+P352-P304+P340-P317-P318-P319-P321-P330-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H312
Germ cell mutagenicity	Muta.	2	H341
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	2	H300

Discovery and Applications

Trabectedin, originally designated ET-743, was isolated from the Caribbean tunicate Ecteinascidia turbinata in the late 1980s. Its discovery resulted from bioprospecting efforts to find novel marine-derived compounds with anticancer properties. Trabectedin stood out for its unique mechanism of action, distinct from traditional cytotoxic agents, targeting DNA repair mechanisms and transcription regulation.

Trabectedin has demonstrated efficacy in the treatment of advanced soft tissue sarcomas, including liposarcoma and leiomyosarcoma, as well as ovarian cancer, particularly in patients with platinum-sensitive disease. Its ability to inhibit transcription factors, such as FUS-CHOP in myxoid liposarcoma, makes it particularly effective against certain subtypes of sarcomas. Trabectedin has also shown activity against recurrent ovarian cancer when used in combination with pegylated liposomal doxorubicin. Additionally, trabectedin exhibits immunomodulatory effects, enhancing the antitumor activity of immune cells within the tumor microenvironment. Despite its efficacy, trabectedin is associated with notable side effects, including myelosuppression and hepatotoxicity, requiring careful patient monitoring. Ongoing research aims to elucidate its role in combination therapies and explore its potential in other cancer types, highlighting trabectedin as a valuable option for patients with challenging-to-treat malignancies.

References

2024. Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes. Nature Communications.
DOI: 10.1038/s41467-024-45664-7

2024. Mechanism of efficacy of trabectedin against myxoid liposarcoma entails detachment of the FUS-DDIT3 transcription factor from its DNA binding sites. Journal of experimental & clinical cancer research: CR.
DOI: 10.1186/s13046-024-03228-z

2024. HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study. Cellular and molecular life sciences: CMLS.
DOI: 10.1007/s00018-024-05250-y