Chemical genetic approaches to probing cell death.

Abstract

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.

• Authors: Nidhi M Gangadhar, Brent R Stockwell
• Journal: Current opinion in chemical biology (Curr Opin Chem Biol) Vol. 11 Issue 1 Pg. 83-7 (Feb 2007) ISSN: 1367-5931 [Print] England
• PMID: 17174591 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

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

Topics

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