UCN-01 (7-hydroxystaurosporine) and other indolocarbazole compounds: a new generation of anti-cancer agents for the new century?

Abstract

UCN-01 (7-hydroxystaurosporine) is a protein kinase inhibitor which is under development as an anti-cancer agent in the USA and Japan. Although UCN-01 was originally isolated from the culture broth of Streptomyces sp. as a protein kinase C-selective inhibitor, its ultimate target as an anti-cancer agent remains elusive. As a single agent, UCN-01 exhibits two key biochemical effects, namely accumulation of cells in the G1 phase of the cell cycle and induction of apoptosis. Both these effects may be important for its anti-cancer activity. As a modulator, UCN-01 enhances the cytotoxicity of other anti-cancer drugs such as DNA-damaging agents and anti-metabolite drugs through putative abrogation of G2 and/or S phase accumulation induced by these anti-cancer agents. Currently, in addition to UCN-01, four other indolocarbazole anti-cancer drugs-two protein kinase inhibitors, CGP 41251, CEP-751, and two DNA-damaging agents, NB-506 and a Rebeccamycin analog-are undergoing clinical investigations in the USA, Europe or Japan. In this review, we would like to address the differences and similarities of these indolocarbazole compounds as anti-cancer agents with regard to their mechanism(s) of action, the effects on cell cycle progression, induction of apoptosis and modulation of drug sensitivity.

• Authors: S Akinaga, K Sugiyama, T Akiyama
• Journal: Anti-cancer drug design (Anticancer Drug Des) Vol. 15 Issue 1 Pg. 43-52 (Feb 2000) ISSN: 0266-9536 [Print] United States
• PMID: 10888035 (Publication Type: Journal Article, Review)

Chemical References

• Alkaloids
• Antineoplastic Agents
• Enzyme Inhibitors
• 7-hydroxystaurosporine
• Staurosporine

Topics

• Alkaloids (pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• DNA Damage
• Enzyme Inhibitors (pharmacology)
• Humans
• Staurosporine (analogs & derivatives)