Abstract
Overexpression of PRL phosphatases (PRL1, PRL2, and PRL3) has been found in a variety of late-stage tumors and their distant metastatic sites. Therefore, the oncogenic PRL phosphatases represent intriguing targets for cancer therapy. There is considerable interest in identifying small molecule inhibitors targeting PRLs as novel anticancer agents. However, it has been difficult to acquire phosphatase activity-based PRL inhibitors due to the unusual wide and shallow catalytic pockets of PRLs revealed by crystal structure studies. Here, we present a novel method to identify PRL1 inhibitors by targeting the PRL1 trimer interface and the procedure to characterize their biochemical and cellular activity.
Keywords:
MTT assay; PRL phosphatases; Transwell migration assay; Trimerization; Virtual screening; Wound healing assay.
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Cycle Proteins / metabolism*
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Drug Discovery
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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HEK293 Cells
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Humans
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Membrane Proteins / antagonists & inhibitors*
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Membrane Proteins / metabolism*
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Molecular Docking Simulation
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Neoplasms / drug therapy
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Neoplasms / enzymology
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Neoplasms / metabolism
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Protein Multimerization / drug effects*
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Protein Tyrosine Phosphatases / antagonists & inhibitors*
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Protein Tyrosine Phosphatases / metabolism*
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Wound Healing / drug effects
Substances
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Antineoplastic Agents
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Cell Cycle Proteins
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Enzyme Inhibitors
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Membrane Proteins
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Small Molecule Libraries
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PTP4A1 protein, human
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Protein Tyrosine Phosphatases