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

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 optim...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2007-07, Vol.50 (15), p.3412-3415
Main Authors: Chao, Wan-Ru, Yean, Dawn, Amin, Khalid, Green, Carol, Jong, Ling
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Carbazoles - chemical synthesis
Carbazoles - chemistry
Carbazoles - pharmacology
Cell Line, Tumor
Drug Design
Drug Screening Assays, Antitumor
General aspects
Humans
Indoles - chemistry
Medical sciences
Mice
Models, Molecular
Molecular Mimicry
Pharmacology. Drug treatments
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
Signal Transduction
Structure-Activity Relationship
Transplantation, Heterologous
Vegetables - chemistry
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm070040e