Small Molecule Inhibitors of EGFR Ectodomain for Breast Cancer Therapy

Abstract

During the reported period, the designed EGFR ectodomain inhibitor has been tested for inhibition of EGFR phosphorylation and growth of breast cancer cells in vitro and in vivo. The compound has been shown to inhibit EGF induced phosphorylation of EGFR in EGFR over expressing NE91 cells. Strong inhibitory effect of the compound against MDA-MB-468 cells has been demonstrated in a poly-HEMA assay. The compound effectively inhibited tumor growth in mice with MDA-MB-468 xenografts and had a moderate effect in MDA-MB-231 xenografts in vivo. Crystallization studies have produced two types of EGFR crystals suitable for soaking experiments with the inhibitory compounds. A number of structural analogs have been designed and are currently being tested for receptor binding and biological activity.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2009
Accession Number
ADA518889

Entities

People

  • Alan Berezov

Organizations

  • University of Pennsylvania

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cells
  • Crystal Structure
  • Crystallization
  • Crystallography
  • Crystals
  • Inhibition
  • Inhibitors
  • Lead Compounds
  • Molecules
  • Neoplasms
  • Phosphorylation
  • Small Molecules
  • Therapy
  • Xenografts

Fields of Study

  • Chemistry

Readers

  • Breast cancer cell signaling and growth regulation.
  • Polymer Science and Engineering.