DIDEMNIN B

Molecular Weight: 1112.35 g/mol
Molecular Formula: C₅₇H₈₉N₇O₁₅

Source: The tunicate Trididemnum solidum (CHORDATA)
Activity: Anti-cancer agent via protein synthesis inhibition
Status: Withdrawn from clinical trials (see below)

Didemnin B was originally isolated from the Caribbean tunicate Trididemnum solidum and first reported in the literature in 1981. Early investigation into the bioactivity of this compound revealed marked antiviral and cytotoxic activity in in vitro tests using standard mouse leukemia cell lines.

Mechanistically, Didemnin B interrupts protein synthesis in target cells by binding non-competitively to palmitoyl protein thioesterase.

Didemnin B was the first defined marine natural product to enter clinical trials as a potential anti-cancer drug. It proceeded through Phase I clinical trials as a prospective anticancer agent and entered into Phase II trials. Although the compound showed promising antitumor, antiviral and immunosuppressive activity, it also exhibited high toxicity, poor solubility, and a short bioactive lifespan. NCI withdrew the drug from clinical trials in the mid-1990s.

Aplidine (Dehydrodidemnin B), a closely related natural product isolated from a different tunicate species, is currently in clinical trials as a potential anti-cancer drug.

Although Didemnin B was never carried into Phase III trials, activity focused on developing the compound as a potential cancer treatment helped pave the way for the rest of the marine-derived products following it into the development pipeline.

NCBI PubChem compound summary page - [ LINK ]

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Kijjoa A and P Sawangwong. 2004. Drugs and cosmetics from the sea (review paper). Mar. Drugs 2004:73-82.

Newman DJ, and GM Cragg. 2004. Advanced preclinical and clinical trials of natural products and related compounds from marine sources. Current Medicinal Chemistry 11:1693-1713.