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Lin H, Xu P, Huang M. Structure-based molecular insights into matrix metalloproteinase inhibitors in cancer treatments. Future Med Chem. 2021;14(1):35-51doi: 10.4155/fmc-2021-0246.
Lin, H., Xu, P., & Huang, M. (2022). Structure-based molecular insights into matrix metalloproteinase inhibitors in cancer treatments. Future medicinal chemistry, 14(1), 35-51. https://doi.org/10.4155/fmc-2021-0246
Lin, Haili, et al. "Structure-based molecular insights into matrix metalloproteinase inhibitors in cancer treatments." Future medicinal chemistry vol. 14,1 (2022): 35-51. doi: https://doi.org/10.4155/fmc-2021-0246
Lin H, Xu P, Huang M. Structure-based molecular insights into matrix metalloproteinase inhibitors in cancer treatments. Future Med Chem. 2022 Jan;14(1):35-51. doi: 10.4155/fmc-2021-0246. Epub 2021 Nov 15. PMID: 34779649.
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Future Med Chem. 2022 Jan;14(1):35-51. doi: 10.4155/fmc-2021-0246. Epub 2021 Nov 15.

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

Future medicinal chemistry

Haili Lin, Peng Xu, Mingdong Huang

Affiliations

  1. Department of Pharmacy, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China.
  2. College of Biological Science & Engineering, Fuzhou University, Fuzhou, China.
  3. College of Chemistry, Fuzhou University, Fuzhou, China.

PMID: 34779649 DOI: 10.4155/fmc-2021-0246

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.

Keywords: inhibitors; matrix metalloproteinases; molecular mechanism; structural biology; urokinase

Publication Types

Grant support