Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase

Bioorg Med Chem. 2002 Nov;10(11):3555-64. doi: 10.1016/s0968-0896(02)00253-5.


The first published synthesis and characterization of a purine-scaffold library of hsp90 inhibitors is presented. The purine-scaffold represents a platform for the creation of easily synthesizable and derivatizable soluble molecules that are amenable for oral administration. The most active compound of the series (71) exhibits binding to hsp90 comparable to the natural product derivative 17AAG that is now in Phase I clinical trial as a cancer therapeutic. Induces the degradation of Her2 tyrosine kinase and arrests the MCF-7 breast cancer cell line at low micromolar concentrations (IC50=2 microM).

Publication types

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

MeSH terms

  • Alkylation
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Cell Division / drug effects
  • Drug Screening Assays, Antitumor
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Peptide Library
  • Protein Binding
  • Purines / chemical synthesis*
  • Purines / chemistry
  • Receptor, ErbB-2 / metabolism*
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • HSP90 Heat-Shock Proteins
  • Indicators and Reagents
  • Peptide Library
  • Purines
  • Receptor, ErbB-2