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Didemnins are cyclic depsipeptide compounds isolated from a tunicate (sea-squirt) of the genus Trididemnum (family of Didemnidæ) that were collected in the Caribbean Sea. They were first isolated in 1978 at the University of Illinois.
Although more than nine didemnins (didemnins A-E, G, X and Y) have been isolated from the extract of Trididemnum solidum, didemnin B is the one that possesses the most potent biological activities. It is a strong antiviral agent against both DNA and RNA viruses such as herpes simplex virus type 1, a strong immunosuppressant that shows some potential in skin graft and is also very cytotoxic. It shows strong activity against murine leukemia cells. Large amounts of didemnin B were chemically synthesized and it was advanced to clinical trials by the National Cancer Institute. It has completed phase II human clinical trials against adenocarcinoma of the kidney, advanced epithelial ovarian cancer, and metastatic breast cancer. Unfortunately, the compound exhibited high toxicity through a high incidence of anaphylactic reactions in patients and trials were terminated.
The didemnin analog aplidine was in phase II clinical trials as of 2003.