Bryostatins
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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 (JSmol)
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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 isolated from the marine organism, Bugula neritina. Bryostatins are potent modulators of protein kinase C. They have been studied in clinical trials as anti-cancer agents, as anti-AIDS/HIV agents and in people with Alzheimer's disease.
Bryostatin 1 is a potent modulator of protein kinase C (PKC).
It showed activity in laboratory tests in cells and model animals, so it was brought into clinical trials. As of 2014 over thirty clinical trials had been conducting, using bryostatin alone and in combination with other agents, in both solid tumors and blood tumors; it did not show a good enough risk:benefit ratio to be advanced further.
It showed enough promise in animal models of Alzheimer's disease that a Phase II trial was started by 2010; the trial was sponsored by the Blanchette Rockefeller Neurosciences Institute. Scientists from that institute started a company called Neurotrope, and launched another clinical trial in Alzheimer's disease, preliminary results of which were released in 2017.
Bryostatin has also been studied in people with HIV.
Bryostatin 1 was 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. As of 2010 20 different bryostatins had been isolated.
The low concentration in bryozoans (to extract one gram of bryostatin, roughly one tonne of the raw bryozoans is needed) makes extraction unviable for large scale production. Due to the structural complexity, total synthesis has proved difficult, with only a few total syntheses reported so far. Total syntheses have been published for bryostatins 1, 2, 3, 7, 9 and 16. Among them, Krische’s total synthesis of bryostatin 7 via C-C bond forming hydrogenation is the shortest synthesis of any bryostatin reported, to date.
A number of structurally simpler synthetic analogs also have been prepared which exhibit similar biological profile and in some cases greater potency, which may provide a practical supply for clinical use.
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