Structure-Based Design of Potent and Selective Inhibitors for Stromelysin-1 and MTI-MMP
Abstract
Matrix metalloproteinases (MMPs) is an important new class of therapeutic targets for the treatment of diseases characterized by excessive extracellular matrix degradation and/or remodeling, such as cancer. The inhibition of the MMPs enzymes can serve as disease-modifying agents. MMPs inhibitors help to prevent cancer metastasis and angiogenesis, and hence help stabilize the disease condition. In this research, we will apply structure- based drug design approach to find novel and selective biological probes of MMPs that may be effective cancer therapies. We have tested and validated the zinc metal ion force field for use in molecular docking, and accurately reproduced the experimental binding free energies for complexes of MMPs. Our docking studies of antineoplastic compounds have identified ligand binding preferences for the MMPs and the compounds selected are currently being assayed. In addition, we have investigated the induced fit mechanism in the active site of MMPs. The information obtained will help us in the next stage of designing diverse and focused combinatorial libraries based on a known and a novel scaffold.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA392520
Entities
People
- Samuel Toba
Organizations
- University of California, San Francisco