BRYOSTATIN 1

Molecular Weight: 905.033 g/mol
Molecular Formula: C₄₇H₆₈O₁₇

Source: The bryozoan Bugula neritina (ECTOPROCTA)
Activity: anti-cancer and immunosuppressive, based on protein kinase C binding inhibition
Status: In Phase II clinical trials.

This natural product was originally extracted from the bryozoan (a sessile, moss-like marine animal) Bugula neritina collected in the Gulf of California and Gulf of Mexico. More recent work has demonstrated that the compound is most likely produced by the microbial symbiont Endobugula sertula. This compound and other bryostatins produced by the microbial associate are exploited by the host as a chemical means of defense, particularly in the larval stage.

Bryostatin 1 is a macrocyclic lactone that belongs to a diverse class of complex products called polyketides. The compound has demonstrated promising anti-cancer, anti-tumor, and immunostimulant activities that are apparently related to its ability to bind to protein kinase C, and enzyme involved in the up-regulating (switching on) and down-regulating (switching off) of certain proteins.

In 2001, Bryostatin 1 was licensed from Arizona State University for commercial development by German pharmaceutical company GPC Biotech and is currently in several Phase II human clinical trials under the guidance of the National Cancer Institutes. That same year, GPC Biotech also struck a licensing deal with Stanford University to develop and commercialize synthetic analogs of Bryostatin 1, known as Bryologs.

The most recent trials have shown that Bryostatin enhances the effectiveness of existing chemotherapies such as taxol and cisplatin, but is relatively ineffective on its own. If Bryostatin proceeds to the development phase, it will likely be developed as a tandem treatment for breast, ovarian and lung cancers and others that respond somewhat to existing regimens. It has an advantage over some current chemotherapies that inhibit red blood cell production and thus require blood transfusions. Bryostatin, in contrast, appears to stimulate red blood cell production.

Bryostatin was granted orphan drug status for use in combination with Taxol for the treatment of esophageal cancer by the FDA in december of 2001. Similar status designation in the EU was awarded in 2002.

Despite the apparent progress, in 2003 GPC Biotech made a strategic decision to discontinue its bryostatin development programs, stating that trials "had not provided sufficient evidence of efficacy combined with an acceptable toxicity profile to move the drug candidate forward."

NCBI PubChem compound summary page - [ LINK ]

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Lopanik N, Lindquist N, Targett N. 2004. Potent cytotoxins produced by a microbial symbiont protect host larvae from predation. Oecologia 139:131-139.

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