Kinetic Analysis of the Inhibition of Matrix Metalloproteinases: Lessons from the Study of Tissue Inhibitors of Metalloproteinases

  • Frances Willenbrock
  • Daniel A. Thomas
  • Augustin Amour
Part of the Methods in Molecular Biology book series (MIMB, volume 622)


Tissue inhibitors of metalloproteinases (TIMPs) are a group of highly potent inhibitors of matrix metalloproteinases (MMPs) and disintegrin metalloproteinases (ADAMs). The high affinity and “tight-binding” nature of the inhibition of MMPs or ADAMs by TIMPs presents challenges for the determination of both equilibrium and dissociation rate constants of these inhibitory events. Methodologies that enable some of these challenges to be overcome are described in this chapter and represent valuable lessons for the in vitro assessment of MMP or ADAM inhibitors within a drug discovery context.

Key words

Matrix metalloproteinases tissue inhibitors of metalloproteinases enzyme kinetics fluorescence resonance energy transfer 


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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Frances Willenbrock
    • 1
  • Daniel A. Thomas
    • 2
  • Augustin Amour
    • 3
  1. 1.OrpingtonKentUK
  2. 2.GlaxoSmithKlineEssexUK
  3. 3.GlaxoSmithKlineHertfordshireUK

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