Xu et al. identified a class of propynoic acid carbamoyl methyl amides that were toxic to several human ovarian cancer cell lines. They showed that one of the most active compounds acted as an irreversible inhibitor of protein disulphide isomerase (PDI) — a chaperone protein found in the endoplasmic reticulum — by forming a covalent bond with the active site cysteines of PDI. The compound suppressed ovarian tumour growth in mice, suggesting that PDI is a novel cancer target and that these PDI inhibitors could serve as a starting point for the development of ovarian cancer therapies.
ORIGINAL RESEARCH PAPER
Xu, S. et al. Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment. Proc. Natl Acad. Sci. USA 109, 16348–16353 (2012)
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Harrison, C. A new target for ovarian cancer. Nat Rev Drug Discov 11, 832 (2012). https://doi.org/10.1038/nrd3885
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DOI: https://doi.org/10.1038/nrd3885