Isolation and structure elucidation of Chlorofusin, a novel p53-MDM2 antagonist from a Fusarium sp

J Am Chem Soc. 2001 Jan 31;123(4):554-60. doi: 10.1021/ja002940p.

Abstract

Wild-type p53 plays a crucial role in the prevention of cancer. Since dysfunction of p53 can be caused by increased levels of the protein MDM2, small molecules which antagonize the interaction between these two proteins have potential in cancer therapy. The discovery and structure determination of a fungal metabolite, chlorofusin, which antagonizes the p53/MDM2 interaction are reported.

Publication types

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

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology
  • Drug Interactions
  • Fungal Proteins / chemistry
  • Fungal Proteins / isolation & purification*
  • Fungal Proteins / pharmacology*
  • Fusarium / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Nuclear Proteins*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / isolation & purification*
  • Peptides, Cyclic / pharmacology*
  • Protein Binding / drug effects
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-mdm2
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antineoplastic Agents
  • Fungal Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Peptides, Cyclic
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • chlorofusin
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2