Computer-aided rational drug design: a novel agent (SR13668) designed to mimic the unique anticancer mechanisms of dietary indole-3-carbinol to block Akt signaling.

Abstract

Indole-3-carbinol (I3C) is a naturally occurring anticancer agent and has entered clinical trials for cancer prevention. However, the clinical development of I3C has been impeded by its poor metabolic profile. The active components of I3C were used to develop a novel class of indole analogs to optimize I3C's anticancer actions, including blocking growth factor-stimulated Akt activation. The most promising of these analogs, SR13668, exhibited potent oral anticancer activity against various cancers and no significant toxicity.

• Authors: Wan-Ru Chao, Dawn Yean, Khalid Amin, Carol Green, Ling Jong
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 50 Issue 15 Pg. 3412-5 (Jul 26 2007) ISSN: 0022-2623 [Print] United States
• PMID: 17602463 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Carbazoles
• Indoles
• SR 13668
• indole-3-carbinol
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Carbazoles (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Drug Design
• Drug Screening Assays, Antitumor
• Humans
• Indoles (chemistry)
• Mice
• Models, Molecular
• Molecular Mimicry
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors)
• Signal Transduction
• Structure-Activity Relationship
• Transplantation, Heterologous
• Vegetables (chemistry)