Yondelis (trabectedin, ET-743): the development of an anticancer agent of marine origin

Anticancer Drugs. 2003 Aug;14(7):487-502. doi: 10.1097/00001813-200308000-00001.


Yondelis (trabectedin, ET-743) is a novel antitumor agent derived from a marine source, the Caribbean tunicate Ecteinascidia turbinata. Preclinical studies demonstrated activity at low concentrations against a variety of tumors. The mechanism by which ET-743 exerts its antitumor activity has not been completely elucidated yet. Binding to the minor groove of DNA which causes a bend towards the major groove has been demonstrated. Furthermore, ET-743 interferes with DNA binding proteins and transcription factors. Clinical studies have been initiated as phase I dose-finding studies at four different treatment regimens. Dose-limiting toxicities were hematological, including neutropenia and thrombocytopenia. Furthermore, significant liver toxicity was observed, especially as a rise in transaminase levels. Antitumor activity in phase I and phase II trials was studied in multiple tumor types, including soft tissue sarcomas, melanomas and breast cancer. ET-743 is currently being extensively investigated in advanced soft tissue sarcomas. The present review describes the development of ET-743, highlighting chemical properties, mode of action, metabolism and preclinical and clinical studies.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating* / adverse effects
  • Antineoplastic Agents, Alkylating* / metabolism
  • Antineoplastic Agents, Alkylating* / therapeutic use
  • Cell Cycle / drug effects
  • Chemistry, Pharmaceutical
  • Clinical Trials as Topic
  • Dioxoles* / adverse effects
  • Dioxoles* / metabolism
  • Dioxoles* / therapeutic use
  • Female
  • Humans
  • Isoquinolines* / adverse effects
  • Isoquinolines* / metabolism
  • Isoquinolines* / therapeutic use
  • Neoplasms / drug therapy*
  • Tetrahydroisoquinolines
  • Trabectedin


  • Antineoplastic Agents, Alkylating
  • Dioxoles
  • Isoquinolines
  • Tetrahydroisoquinolines
  • Trabectedin