Cytochrome P450 1A1-mediated anticancer drug discovery: in silico findings

Expert Opin Drug Discov. 2012 Sep;7(9):771-89. doi: 10.1517/17460441.2012.698260. Epub 2012 Jun 21.


Introduction: Target-specific drugs may offer fewer side/adverse effects in comparison with other anticancer agents and thus save normal healthy cells to a greater extent. The selective overexpression of cytochrome P450 1A1 (CYP1A1) in tumor cells induces the metabolism of benzothiazole and aminoflavone compounds to their reactive species, which are responsible for DNA adduct formation and cell death. This review encompasses the novelty of CYP1A1 as an anticancer drug target and explores the possible in silico strategies that would be applicable in the discovery and development of future antitumor compounds.

Areas covered: This review highlights the various ligand-based and target-based in silico methodologies that were efficiently used in exploration of CYP1A1 as a novel antitumor target. These methodologies include electronic structure analysis, CoMFA studies, homology modeling, molecular docking, molecular dynamics analysis, pharmacophore mapping and quantitative structure activity relationship (QSAR) studies. It also focuses on the various approaches used in the development of the lysyl amide prodrug of 5F-203 (NSC710305) and dimethanesulfonate salt of 5-aminoflavone (NSC710464) as clinical candidates from their less potent analogues.

Expert opinion: Selective overexpression of CYP1A1 in cancer cells offers tumor-specific drug design to ameliorate the current adverse effects associated with existing antitumor agents. Medicinal chemistry and in vitro driven approaches, in combination with knowledge-based drug design and by using the currently available tools of in silico methodologies, would certainly make it possible to design and develop novel anticancer compounds targeting CYP1A1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Computer Simulation
  • Cytochrome P-450 CYP1A1 / metabolism*
  • Drug Discovery / methods
  • Drug Discovery / standards
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology*
  • Quantitative Structure-Activity Relationship


  • Antineoplastic Agents
  • Cytochrome P-450 CYP1A1