Potent inhibitors of equine steroid isomerase EcaGST A3-3


Creative Commons License

Lindstrom H., Mazari A. M. A. , Musdal Y., Mannervik B.

PLOS ONE, vol.14, no.3, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 14 Issue: 3
  • Publication Date: 2019
  • Doi Number: 10.1371/journal.pone.0214160
  • Journal Name: PLOS ONE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Hacettepe University Affiliated: No

Abstract

Equine glutathione transferase A3-3 (EcaGST A3-3) belongs to the superfamily of detoxication enzymes found in all higher organisms. However, it is also the most efficient steroid double-bond isomerase known in mammals. Equus ferus caballus shares the steroidogenic pathway with Homo sapiens, which makes the horse a suitable animal model for investigations of human steroidogenesis. Inhibition of the enzyme has potential for treatment of steroid-hormone-dependent disorders. Screening of a library of FDA-approved drugs identified 16 out of 1040 compounds, which at 10 mu M concentration afforded at least 50% inhibition of EcaGST A3-3. The most potent inhibitors, anthralin, sennoside A, tannic acid, and ethacrynic acid, were characterized by IC50 values in the submicromolar range when assayed with the natural substrate Delta(5)-androstene-3,17-dione.