Trabectedin (ET-743) from marine tunicate for cancer treatment

Abstract

Trabectedin (Yondelis; ET-743) is a DNA binding agent that was originally derived from the marine tunicate Ecteinascidia turbinata and is currently prepared synthetically. Its mechanism of action is different from the conventional alkylating agents used in cancer chemotherapy. Two of the three fused rings of trabectedin molecule are involved in the minor groove binding to DNA; forming DNA adducts on N2 position of guanine, and bends DNA towards the major groove, while the third is known to interact with different transcription factors and DNA-binding proteins. Trabectedin has been found to inhibit the proliferation of various tumor cells in vitro and in vivo. It is the first anticancer marine derived drug that has been approved by the European Union, Russia and South Korea for the treatment of advanced or metastatic soft tissue sarcoma. Several Phase II clinical trials are also going on for several cancer types including breast and prostate.