title: Discovery and Evaluation of PRL Trimer Disruptors for Novel Anticancer Agents.
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.
authors: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA.
authors: Yunpeng
authors: Y
authors: Bai
authors: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA.
authors: Zhi-Hong
authors: ZH
authors: Yu
authors: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA. zyzhang@iu.edu.
authors: Zhong-Yin
authors: ZY
authors: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D054852:Small Molecule Libraries; C490198:PTP4A1 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: MTT assay; PRL phosphatases; Transwell migration assay; Trimerization; Virtual screening; Wound healing assay