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 Academic Article Article uri icon

Overview

MeSH Major

  • Antineoplastic Combined Chemotherapy Protocols
  • HSP90 Heat-Shock Proteins
  • Neoplasms
  • Proto-Oncogene Proteins

abstract

  • 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 date

  • November 2002

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/S0968-0896(02)00253-5

PubMed ID

  • 12213470

Additional Document Info

start page

  • 3555

end page

  • 64

volume

  • 10

number

  • 11