The clinical development of the bryostatins
作者:
A Clamp,
GC Jayson,
期刊:
Anti-Cancer Drugs
(OVID Available online 2002)
卷期:
Volume 13,
issue 7
页码: 673-683
ISSN:0959-4973
年代: 2002
出版商: OVID
关键词: Bryostatin;protein kinase C;signal transduction
数据来源: OVID
摘要:
The bryostatins are a group of novel macrocyclic lactones derived from the marine bryozoan,Bugula neritina.In vitroevidence indicates that their main mechanism of action is modulation of protein kinase C (PKC) activity. Phase I studies suggested significant antineoplastic activity against several tumor types and defined the main dose-limiting toxicity as myalgia. Bryostatin-1 has subsequently been investigated extensively in phase II clinical trials as a single agent, although trial design has been hampered by lack of human pharmacokinetic data. Results have been generally disappointing butin vitroand animal data suggests an important role for bryostatin-1 in combination with cytotoxic agents. Preliminary results of phase I studies support these observations but further work needs to be done to define the future role of the bryostatins in the clinic.
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