Didemnin B

Abstract

A new class of marine compounds, the didemnins, with potent antitumor activity has been identified. They share the novel structure of a cyclic depsipeptide. Among three structurally related compounds, didemnin B is by far the most potent in its in vitro cytotoxicity and in vivo antitumor activity (0.001 microgram/ml inhibits the growth of L1210 leukemia cells by 50%). It also demonstrates good antitumor activity against B16 melanoma and moderate activity against M5076 sarcoma and P388 leukemia. The compound also has good antiviral and potent immunosuppressive properties. Although the precise mechanism of action for the cytotoxicity remains unknown, the agent inhibits protein synthesis more than DNA synthesis and the inhibition of protein synthesis is closely correlated with inhibition of L1210 cell growth. Toxicology studies in CD2F1 mice, Fischer 344 rats and beagle dogs reveal that major target organs are the lymphatics, gastrointestinal tract, liver and kidney. Phase I trials are currently in progress under the auspices of the National Cancer Institute.

Marine Natural Products: A New Wave of Drugs?

“…Elongation factor 1α is one of the targets for didemnin B [33], the first marine compound where natural material was used for clinical trials as an anticancer drug [34]. Although this compound is no longer in clinical trials due to its side effects [35], its closely related analogue plitidepsin (Aplidin ® ) has successfully reached Phase II clinical trials as an anticancer agent [9].…”

Macrocyclic N-Methylated Cyclic Peptides and Depsipeptides

“…These compounds were isolated from a tunicate, genus Trididemnum, where didemnin A 175 and B 176 are the two major components (Fig. One of these compounds, didemnin B 176 is the first marine natural product that has gone through clinical trials [118][119][120][121][122]. They have some interesting biological activities including antitumor, antiviral [116], and immunosuppressive activities [117].…”

Marine Peptide Secondary Metabolites

“…Didemnin B (Rinehart et al, 1981) occupies a particular place in the world of MNPs, being the first marine natural product to enter clinical trials against cancer in the US (Chun et al, 1986). Unfortunately, however, its development was halted because of important adverse side effects.…”