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PDBsum entry 6a8g
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Hydrolase inhibitor/hydrolase
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PDB id
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6a8g
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References listed in PDB file
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Key reference
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Title
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Suppression of tumor growth and metastases by targeted intervention in urokinase activity with cyclic peptides.
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Authors
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D.Wang,
Y.Yang,
L.Jiang,
Y.Wang,
J.Li,
P.A.Andreasen,
Z.Chen,
M.Huang,
P.Xu.
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Ref.
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J Med Chem, 2019,
62,
2172-2183.
[DOI no: ]
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PubMed id
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Abstract
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Urokinase-type plasminogen activator (uPA) is a diagnostic marker for breast and
prostate cancers recommended by American Society for Clinical Oncology and
German Breast Cancer Society. Inhibition of uPA was proposed as an efficient
strategy for cancer treatments. In this study, we report peptide-based uPA
inhibitors with high potency and specificity comparable to monoclonal
antibodies. We revealed the binding and inhibitory mechanisms by combining
crystallography, molecular dynamic simulation, and other biophysical and
biochemical approaches. Besides, we showed that our peptides efficiently
inhibited the invasion of cancer cells via intervening with the processes of the
degradation of extracellular matrices. Furthermore, our peptides significantly
suppressed the tumor growth and the cancer metastases in tumor-bearing mice.
This study demonstrates that these uPA peptides are highly potent anticancer
agents and reveals the mechanistic insights of these uPA inhibitors, which can
be useful for developing other serine protease inhibitors.
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