Challenges to the development of bryostatin-type anticancer drugs based on the activation mechanism of protein kinase Cδ

Medicinal Research Reviews
Kazuhiro IrieYu Nakagawa


Protein kinase C (PKC) isozymes are widely recognized as targets for anticancer therapy, and recent investigations demonstrated that PKC activators are potential therapeutic candidates for Alzheimer's disease and acquired immune deficiency syndrome. However, concerns exist about their therapeutic uses because most PKC activators are potent tumor promoters. Bryostatin 1 (bryo-1) is a unique PKC activator with little tumor-promoting activities. Bryo-1 is currently undergoing clinical trials for the treatment of cancer. However, its limited availability from natural sources and difficulty in the synthesis hamper further studies on its mode of action and structural optimization. Although excellent practical methods for synthesizing several bryo-1-related compounds have been developed, the identification of synthetically more accessible compounds with bryo-1-like activity also provides a promising way to circumvent the problem of supply. The authors focused on the bryo-1's unique mechanism of activating PKCδ that plays a tumor suppressor role, and found that a simple and less lipophilic analogue (aplog-1) of the tumor-promoting aplysiatoxin showed PKCδ-activating behavior similar to bryo-1. Aplog-1 was easily synthesized in only 22 ...Continue Reading


Feb 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·H zur HausenE Hecker
May 29, 1992·Journal of Medicinal Chemistry·K R GustafsonJ A Beutler
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·Y OnoY Nishizuka
Jan 1, 1987·Advances in Cancer Research·H Fujiki, T Sugimura
Nov 1, 1987·Immunobiology·H MohrA Plessing-Menze
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·P A WenderP M Blumberg
Mar 1, 1966·Journal of Bacteriology·G Henle, W Henle
Jan 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·P A WenderB L Miller
Jul 1, 1996·Toxicon : Official Journal of the International Society on Toxinology·H NagaiY Hokama
Jun 1, 1997·Molecular and Cellular Biology·Z LuD A Foster
Nov 21, 1998·British Journal of Cancer·D J PropperA L Harris
Feb 24, 2001·Bioscience, Biotechnology, and Biochemistry·K IrieP A Wender
Jul 27, 2001·Biochemical and Biophysical Research Communications·G ZhuR O Messing
Feb 22, 2002·Cancer Chemotherapy and Pharmacology·Beverly A TeicherMargaret M Faul
Aug 28, 2002·Natural Product Reports·Karl J HaleMark Frigerio
Sep 13, 2002·Bioscience, Biotechnology, and Biochemistry·Akiko MasudaHajime Ohigashi
Nov 15, 2002·Journal of the American Chemical Society·Paul A WenderTim M Turner
Dec 10, 2002·Science·G ManningS Sudarsanam
Apr 1, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Desmond N Jackson, David A Foster

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