Format

Send to

Choose Destination
Drug Discov Today. 2014 Mar;19(3):222-40. doi: 10.1016/j.drudis.2013.10.017. Epub 2013 Oct 31.

Protein disulfide isomerase: a promising target for cancer therapy.

Author information

1
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.
2
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089, USA.
3
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.

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.

PMID:
24184531
DOI:
10.1016/j.drudis.2013.10.017
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center