17AAG: Low target binding affinity and potent cell activity - Finding an explanation Academic Article uri icon


MeSH Major

  • Breast Neoplasms
  • Prostatic Neoplasms
  • Rifabutin


  • The ansamycin geldanamycin (GM) and its derivative, 17AAG, now in early clinical trials in cancer patients, have potent activity against several cancer cells at low nanomolar concentrations. The main target of these drugs is the molecular chaperone heat shock protein 90. Contrary to the high antitumor potency, the affinity of these drugs for the chaperone was determined to be approximately 1 microM. We propose that this difference can partly be explained by the physicochemical characteristics of the ansamycins. GM and 17AAG accumulate in cells, producing higher intracellular concentrations than expected. We conclude that although apparent activity for ansamycins can be seen at low nanomolar concentration, their real activity correlates with the heat shock protein 90 binding affinity and is in the low micromolar concentration range. We suggest that in the clinic, micromolar concentrations of 17AAG must accumulate in the tumor cells to achieve antitumor effects in patients comparable with ones achieved in tissue culture settings.

publication date

  • February 2003



  • Academic Article



  • eng

PubMed ID

  • 12589029

Additional Document Info

start page

  • 123

end page

  • 9


  • 2


  • 2