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Trabectedin
Trabectedin (also known as ecteinascidin 743 or ET-743) is an anti-tumor drug. It is sold by Zeltia and Johnson and Johnson under the brand name Yondelis. 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.
==Discovery and production==
During the 1950s and 1960s, the National Cancer Institute carried out a wide ranging program of screening plant and marine organism material. As part of that program extract from the sea squirt ''Ecteinascidia turbinata'' was found to have anticancer activity in 1969.
Separation and characterisation of the active molecules had to wait many years for the development of sufficiently sensitive techniques, and the structure of one of them, Ecteinascidin 743, was determined by KL Rinehart at the University of Illinois in 1984. Rinehart had collected his sea squirts by scuba diving in the reefs of the West Indies. Recently, the biosynthetic pathway responsible for producing the drug has been determined to come from ''Candidatus Endoecteinascidia frumentensis'', a microbial symbiont of the tunicate.
The Spanish company PharmaMar licensed the compound from the University of Illinois before 1994 and attempted to farm the sea squirt with limited success.〔 Yields from the sea squirt are extremely low - it takes 1 tonne of animals to isolate 1 gram of trabectedin - and about 5 grams were believed to be needed for a clinical trial so Rinehart asked the Harvard chemist E. J. Corey to search for a synthetic method of preparation. His group developed such a method and published it in 1996. This was later followed by a simpler and more tractable method which was patented by Harvard and subsequently licensed to PharmaMar.〔 The current supply is based on a semisynthetic process developed by PharmaMar starting from safracin B, an antibiotic obtained by fermentation of the bacterium ''Pseudomonas fluorescens''. PharmaMar have entered into an agreement with Johnson & Johnson to market the compound outside Europe.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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