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Methods Mol Biol. 2016;1447:121-38. doi: 10.1007/978-1-4939-3746-2_8.

Discovery and Evaluation of PRL Trimer Disruptors for Novel Anticancer Agents.

Author information

1
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA.
2
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA. zyzhang@iu.edu.

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

PMID:
27514804
DOI:
10.1007/978-1-4939-3746-2_8
[Indexed for MEDLINE]

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