Development of Targeted Ansamycins as Novel Antiestrogens and Tyrosine Kinase Inhibitors.

Abstract

The subject of this grant is the development of a novel class of anticancer agents that induces the degradation of specific proteins by causing them to bind in a stable complex with the chaperone molecule Hsp90. This is accomplished by synthesizing hybrid drugs comprised of the Hsp90-binding drug geldanamycin covalently joined to a high affinity ligand for the protein to be degraded. The goal of this grant was to pilot this idea by making geldanamycin- estrogen hybrids to target the estrogen receptor. We have succeeded in synthesizing a family of such hybrids, in determining characteristics of the linker moiety required for activity and in identifying a selective compound with selective cytotoxic activity against ER-containing MCF-7 breast cancer cells.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 1998
Accession Number
ADA369205

Entities

People

  • Neal Rosen

Organizations

  • Memorial Sloan Kettering Cancer Center

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Antineoplastic Agents
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Culture Techniques
  • Estrogens
  • Inhibitors
  • Molecules
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • Steady State
  • Tumor Cell Line
  • Tyrosine

Fields of Study

  • Chemistry

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and Cellular Biochemistry