Identification of Natural Product Sulfuretin Derivatives as Inhibitors for the Endoplasmic Reticulum Redox Protein ERO1α.

ABSTRACT: The flavin adenine dinucleotide containing Endoplasmic Reticulum Oxidoreductase-1 α (ERO1α) catalyzes the formation of de novo disulfide bond formation of secretory and transmembrane proteins and contributes towards proper protein folding. Recently, increased ERO1α expression has been shown to contribute to increased tumor growth and metastasis in multiple cancer types. In this report we sought to define novel chemical space for targeting ERO1α function. Using the previously reported ERO1α inhibitor compound, EN-460, as a benchmark pharmacological tool we were able to identify a sulfuretin derivative, T151742 which was approximately two-fold more potent using a recombinant enzyme assay system (IC₅₀ = 8.27 ± 2.33 μM) compared to EN-460 (IC₅₀= 16.46 ± 3.47 μM). A

SUBMITTER: Johnson BD 

PROVIDER: S-EPMC9312093 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature