ET-743 (PharmaMar/NCI/Ortho Biotech).
Ecteinascidin-743 (ET-743), a tetrahydroisoquinoline alkaloid isolated from the Caribbean tunicate, Ecteinascidia turbinata, is under development by PharmaMar (the pharmaceutical subsidiary of Zeltia), the National Cancer Institute (NCI) and Ortho Biotech, as a potential treatment for several tumor types including breast cancer, lung cancer, ovarian cancer and melanoma. It appears to function by DNA minor groove alkylation, which induces topoisomerase I-mediated protein-linked DNA strand breakage [322446]. ET-743 is an analog of ET-729 [169825]. As of February 1999, it was in phase II trials [326363], [326268], [375811] and, in August 2001, PharmaMar expected phase II trials for breast, ovarian and non-small cell lung cancer to be completed by August 2002 [423408]. In June 2001, the EMEA awarded ET-743 Orphan Drug status for the treatment of soft tissue sarcoma [412446]. The orphan medicinal product designation is designed to expedite the registration of pharmaceuticals for life-threatening or debilitating conditions with low prevalence (< 5 per 10,000 in the EU), for which no satisfactory treatment exists. The designation offers the sponsor several incentives, such as centralized procedure review of the Marketing Authorization Application and, upon approval, ten-year marketing exclusivity throughout Europe for the therapeutic indication for which it was granted. PharmaMar is also collaborating with the European Organization for Research and Treatment of Cancer (EORTC); PharmaMar has obtained the worldwide rights to ET-743, amongst other ecteinascidins, from the University of Illinois [177268]. In August 2001, Dresdner Kleinwort Wasserstein predicted total sales, for all ET-743's indications, of $1 million in 2002, rising through $1106 million in 2007 to $2725 million in 2011 [423408].
Verschraegen
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University of Texas, MD Anderson Cancer Center, Houston 77030, USA. cverschr@mail.mdanderson.org
Glover
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D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004149:Dioxoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin
D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin