Bryostatin
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IUPAC name
(1S,3S,5Z,7R,8E,11S,12S,13E,15S,17R,20R,23R,25S)-25-Acetoxy-1,11,20-trihydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis(2-methoxy-2-oxoethylidene)-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.13,7.111,15]nonacos-8-en-12-yl (2E,4E)-2,4-octadienoate
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3D model (Jmol)
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| C47H68O17 | |
| Molar mass | 905.04 g·mol−1 |
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Bryostatins are a group of macrolide lactones first isolated in the 1960s by George Pettit from extracts of a species of bryozoan, Bugula neritina based on research from samples originally provided by Jack Rudloe to Jonathan L. Hartwell’s anticancer drug discovery group at the National Cancer Institute (NCI). The structure of bryostatin 1 was determined in 1982. To date 20 different bryostatins have been isolated; further, certain analogs of bryostatin have been referred to as "bryologs". Bryostatins are potent modulators of protein kinase C. They are currently under investigation as anti-cancer agents, as anti-AIDS/HIV agents and as a memory-enhancing agent.
Bryostatin 1 is a potent modulator of protein kinase C (PKC). Short-term effects of bryostatin 1 include activation of classical or conventional PKCs and novel PKCs, whereas prolonged presence leads to lowered PKC activation. Bryostatin 1 effects on different isoforms of PKC vary. In in vitro tests bryostatin 1 was able to inhibit cell growth and angiogenesis and to excite cell differentiation and apoptosis. Bryostatin also shows immunomodulatory properties.
In in vitro trials bryostatin 1 was able to induce apoptosis in HL-60 chronic lymphocytic leukaemia. It could be shown that bryostatin 1 acts synergistically in combination with other anti-cancer drugs. Drug combination was effective against a large variety of tumor cells including lung, prostate and non-Hodgkin's lymphoma tumor cells. Although animal studies were promising, bryostatin 1 as a single drug has failed to demonstrate significant activity in tumor patients in phase II trials in a wide range of tumor types, including melanoma and colorectal cancer. Additionally severe side-effects, mainly myalgia, were observed after bryostatin administration. As a consequence research focus has shifted to an investigation of combination therapy with other chemotherapeutic antitumor agents such as gemcitabine, vincristine, cisplatin, and paclitaxel. As of 2016[update] about 30 clinical trials for various cancers have been completed.
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