Identification of a geldanamycin dimer that induces the selective degradation of HER-family tyrosine kinases Academic Article uri icon

Overview

MeSH Major

  • Antibiotics, Antineoplastic
  • Breast Neoplasms
  • Quinones
  • Receptor, ErbB-2

abstract

  • Geldanamycin (GM) is a natural antibiotic that binds Hsp90 and induces the degradation of receptor tyrosine kinases, steroid receptors, and Raf. It is a potent inhibitor of cancer cells that overexpress HER-kinases, but its effects on other important proteins may cause significant toxicity and limit its clinical use. We report the synthesis and identification of a GM dimer, GMD-4c, which had selective activity against HER-kinases. Selectivity was a function of linker length and required two intact GM moieties. GMD-4c is a potent inducer of G1 block and apoptosis of breast cancer cell lines that overexpress HER2, but does not appreciably inhibit the growth of 32D cells that lack HER-kinases. GMD-4c could be useful in the treatment of carcinomas dependent on HER-kinases.

publication date

  • April 15, 2000

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 10786665

Additional Document Info

start page

  • 2090

end page

  • 4

volume

  • 60

number

  • 8