Structure-Based Design of erbB-2 Selective Small Molecule Kinase Inhibitors

Abstract

Experimental 3D structure (including the kinase domain) of either erbB-2 or EGFR has not been determined. Fortunately, the structures of the kinase domain of a number of receptor tyrosine kinases have been determined through X-ray crystallography with high resolutions. Protein kinases, including erbB-2 and EGFR, have an active and inactive conformation. Analysis of the X-ray structures of several kinases, including insulin receptor kinase and FGFR kinase showed that when an ATP analog or a small molecule kinase inhibitor bound to the ATP binding site of the kinase domain, the kinase always assumes an active conformation. Accordingly, it is hypothesized that erbB-2 and EGFR also assume an active conformation when bound to an inhibitor.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2001
Accession Number
ADA400496

Entities

People

  • Shaomeng Wang

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biological Products
  • Breast Cancer
  • Cell Line
  • Cells
  • Crystallography
  • High Resolution
  • Inhibition
  • Inhibitors
  • Lead Compounds
  • Molecular Dynamics
  • Molecules
  • Neoplasms
  • Simulations
  • Small Molecules
  • X Rays
  • X-Ray Crystallography

Fields of Study

  • Chemistry

Readers

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