title: Protein disulfide isomerase: a promising target for cancer therapy.
abstract: Protein disulfide isomerase (PDI) has a key role in maintaining cellular homeostasis by mediating oxidative protein folding. It catalyzes disulfide bond formation, breakage and rearrangement in the endoplasmic reticulum and has chaperone protein activity. Increasing evidence suggests that PDI supports the survival and progression of several cancers. During the past decade, robust PDI activity assays have been developed and several PDI inhibitors identified, but none has been approved for clinical use. Herein, we review current knowledge of the role of PDI in cancer and discuss various assays for measuring the activities of PDI, highlighting their sensitivities and usefulness for high-throughput screening. The previously reported PDI inhibitors require further validation to serve as bona fide leads and additional optimization to generate novel drug candidates for clinical studies.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy and Translational Oncology Program, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Building 520, Ann Arbor, MI 48109, USA.
authors.forename: Shili
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089, USA.
authors.forename: Saranya
authors.initials: S
authors.lastname: Sankar
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy and Translational Oncology Program, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Building 520, Ann Arbor, MI 48109, USA. Electronic address: neamati@umich.edu.
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018450:Disease Progression; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017510:Protein Folding
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019704:Protein Disulfide-Isomerases