Structure-based molecular insights into matrix metalloproteinase inhibitors in cancer treatments.

Abstract

Protease inhibitors are of considerable interest as anticancer agents. Matrix metalloproteinases (MMPs) were the earliest type of proteases considered as anticancer targets. The developments of MMP inhibitors (MMPIs) by pharmaceutical companies can be dated from the early 1980s. Thus far, none of the over 50 MMPIs entering clinical trials have been approved. This work summarizes the reported studies on the structure of MMPs and complexes with ligands and inhibitors, based on which, the authors analyzed the clinical failures of MMPIs in a structural biological manner. Furthermore, MMPs were systematically compared with urokinase, a protease-generating plasmin, which plays similar pathological roles in cancer development; the reasons for the clinical successes of urokinase inhibitors and the clinical failures of MMPIs are discussed.

• Authors: Haili Lin, Peng Xu, Mingdong Huang
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 14 Issue 1 Pg. 35-51 (01 2022) ISSN: 1756-8927 [Electronic] England
• PMID: 34779649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Hydroxamic Acids
• Matrix Metalloproteinase Inhibitors
• Tissue Inhibitor of Metalloproteinases
• Urokinase-Type Plasminogen Activator
• Matrix Metalloproteinases

Topics

• Binding Sites
• Catalytic Domain
• Humans
• Hydroxamic Acids (chemistry, metabolism, therapeutic use)
• Matrix Metalloproteinase Inhibitors (chemistry, metabolism, therapeutic use)
• Matrix Metalloproteinases (chemistry, metabolism)
• Molecular Dynamics Simulation
• Neoplasms (drug therapy, metabolism, pathology)
• Tissue Inhibitor of Metalloproteinases (chemistry, metabolism)
• Urokinase-Type Plasminogen Activator (metabolism, therapeutic use)