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

J Med Chem. 2007 Jul 26;50(15):3412-5. doi: 10.1021/jm070040e. Epub 2007 Jun 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Carbazoles / chemical synthesis
  • Carbazoles / chemistry*
  • Carbazoles / 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*


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