Inhibitory Antibodies Designed for Matrix Metalloproteinase Modulation

Molecules. 2019 Jun 18;24(12):2265. doi: 10.3390/molecules24122265.

Abstract

The family of matrix metalloproteinases (MMPs) consists of a set of biological targets that are involved in a multitude of severe pathogenic events such as different forms of cancers or arthritis. Modulation of the target class with small molecule drugs has not led to the anticipated success until present, as all clinical trials failed due to unacceptable side effects or a lack of therapeutic outcome. Monoclonal antibodies offer a tremendous therapeutic potential given their high target selectivity and good pharmacokinetic profiles. For the treatment of a variety of diseases there are already antibody therapies available and the number is increasing. Recently, several antibodies were developed for the selective inhibition of single MMPs that showed high potency and were therefore investigated in in vivo studies with promising results. In this review, we highlight the progress that has been achieved toward the design of inhibitory antibodies that successfully modulate MMP-9 and MMP-14.

Keywords: drug design; inhibitory antibody; matrix metalloproteinase; selectivity; tissue inhibitors of metalloproteinases.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / pharmacology*
  • Binding Sites
  • Drug Design*
  • Humans
  • Matrix Metalloproteinase Inhibitors / chemistry*
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Matrix Metalloproteinases / chemistry*
  • Matrix Metalloproteinases / classification
  • Molecular Conformation
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Antibodies, Monoclonal
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases

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