Chemical genetic approaches to probing cell death

Curr Opin Chem Biol. 2007 Feb;11(1):83-7. doi: 10.1016/j.cbpa.2006.11.033. Epub 2006 Dec 14.


Chemical genetics has arisen as a tool for the discovery of pathways and proteins in mammalian systems. This approach, comprising small-molecule screening combined with biochemical and genomic target identification methods, enables one to assess which proteins are involved in regulating a particular phenotype. Applied to cell death, this strategy can reveal novel targets and pathways regulating the demise of mammalian cells. Numerous diseases have been linked to the loss of regulation of cell death. Defining the mechanisms governing cell death in these diseases might lead to the discovery of therapeutic agents and targets and provide a richer understanding of the mortality of living systems. Recent advances include the discovery of novel small molecules regulating cell death pathways -- necrostatin and erastin -- as well as the elucidation of the mechanism of death induced in cancer cells by the cytotoxic agent Apratoxin A.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects*
  • Cell Death / physiology
  • Cell Line, Tumor
  • Depsipeptides / pharmacology
  • Genetic Techniques*
  • Genome
  • Humans
  • Imidazoles / pharmacology
  • Indoles / pharmacology
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Pharmaceutical Preparations
  • Phenotype
  • Piperazines / pharmacology
  • Proteins* / chemistry
  • Proteins* / genetics
  • Proteins* / metabolism


  • Antineoplastic Agents
  • Depsipeptides
  • Imidazoles
  • Indoles
  • Pharmaceutical Preparations
  • Piperazines
  • Proteins
  • apratoxin A
  • erastin
  • necrostatin-1