UNIT 3.7 Characterization of Matrix Metalloproteinase Inhibitors: Enzymatic Assays

  1. Patrick A. Marcotte,
  2. Steven K. Davidsen

Published Online: 1 AUG 2001

DOI: 10.1002/0471141755.ph0307s13

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

Marcotte, P. A. and Davidsen, S. K. 2001. Characterization of Matrix Metalloproteinase Inhibitors: Enzymatic Assays. Current Protocols in Pharmacology. 13:3.7:3.7.1–3.7.13.

Author Information

  1. Abbott Laboratories, Abbott Park, Illinois

Publication History

  1. Published Online: 1 AUG 2001
  2. Published Print: JUN 2001


The matrix metalloproteinases (MMPs) are a family of tightly regulated proteases that are involved in the catabolic aspect of remodeling and maintenance of normal tissue, and more than 20 human MMPs have been identified thus far. The MMPs collectively degrade a broad range of protein components of the extracellular matrix. While some substrate overlap exists, individual MMPs have been shown to process certain substrates more efficiently than others. These differences raise the critical issue of whether broad-spectrum inhibitors, active against all MMPs, or selective inhibitors, targeted to a subset of enzymes, represent the optimal therapeutic strategy for a given disease. This suggests the need to assess the inhibition potency of test compounds across a range of MMP family members. Described in this unit is a method for the in vitro characterization of MMP inhibitors. The Basic Protocol is used to determine the potency of test compounds as inhibitors of 8 representative MMPs through the measurement of their inhibition of cleavage of a fluorogenic substrate. Since this substrate is efficiently hydrolyzed by all MMPs in the screening assays presented here, the method is convenient for assessing the selectivity of inhibitors against multiple enzymes. A describes the activation of MMP zymogens.