Targeting wide-range oncogenic transformation via PU24FCl, a specific inhibitor of tumor Hsp90.

Journal Article (Journal Article)

Agents that inhibit Hsp90 function hold significant promise in cancer therapy. Here we present PU24FCl, a representative of the first class of designed Hsp90 inhibitors. By specifically and potently inhibiting tumor Hsp90, PU24FCl exhibits wide-ranging anti-cancer activities that occur at similar doses in all tested tumor types. Normal cells are 10- to 50-fold more resistant to these effects. Its Hsp90 inhibition results in multiple anti-tumor-specific effects, such as degradation of Hsp90-client proteins involved in cell growth, survival, and specific transformation, inhibition of cancer cell growth, delay of cell cycle progression, induction of morphological and functional changes, and apoptosis. In concordance with its higher affinity for tumor Hsp90, in vivo PU24FCl accumulates in tumors while being rapidly cleared from normal tissue. Concentrations achieved in vivo in tumors lead to single-agent anti-tumor activity at non-toxic doses.

Full Text

Duke Authors

Cited Authors

  • Vilenchik, M; Solit, D; Basso, A; Huezo, H; Lucas, B; He, H; Rosen, N; Spampinato, C; Modrich, P; Chiosis, G

Published Date

  • June 2004

Published In

Volume / Issue

  • 11 / 6

Start / End Page

  • 787 - 797

PubMed ID

  • 15217612

International Standard Serial Number (ISSN)

  • 1074-5521

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2004.04.008


  • eng

Conference Location

  • United States