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Thériault JF, Poirier D, Lin SX. The multi-specific human 17 beta-hydroxysteroid dehydrogenase type 7: Non-competitive inhibitors can target different catalyses to facilitate breast cancer treatment. J Steroid Biochem Mol Biol. 2021;214:105963doi: 10.1016/j.jsbmb.2021.105963.
Thériault, J. F., Poirier, D., & Lin, S. X. (2021). The multi-specific human 17 beta-hydroxysteroid dehydrogenase type 7: Non-competitive inhibitors can target different catalyses to facilitate breast cancer treatment. The Journal of steroid biochemistry and molecular biology, 214105963. https://doi.org/10.1016/j.jsbmb.2021.105963
Thériault, Jean-Francois, et al. "The multi-specific human 17 beta-hydroxysteroid dehydrogenase type 7: Non-competitive inhibitors can target different catalyses to facilitate breast cancer treatment." The Journal of steroid biochemistry and molecular biology vol. 214 (2021): 105963. doi: https://doi.org/10.1016/j.jsbmb.2021.105963
Thériault JF, Poirier D, Lin SX. The multi-specific human 17 beta-hydroxysteroid dehydrogenase type 7: Non-competitive inhibitors can target different catalyses to facilitate breast cancer treatment. J Steroid Biochem Mol Biol. 2021 Nov;214:105963. doi: 10.1016/j.jsbmb.2021.105963. Epub 2021 Aug 13. PMID: 34400276.
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J Steroid Biochem Mol Biol. 2021 Nov;214:105963. doi: 10.1016/j.jsbmb.2021.105963. Epub 2021 Aug 13.

The multi-specific human 17 beta-hydroxysteroid dehydrogenase type 7: Non-competitive inhibitors can target different catalyses to facilitate breast cancer treatment.

The Journal of steroid biochemistry and molecular biology

Jean-Francois Thériault, Donald Poirier, Sheng-Xiang Lin

Affiliations

  1. Endocrinology and Nephrology, CHU de Quebec-Research Center (CHUL), 2705 Boulevard Laurier, Québec City, Québec, G1V 4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, 1050 avenue de la Médecine, Québec City, Québec, G1V 0A6, Canada; Centre de recherche sur le cancer de l'Université Laval, 9, rue McMahon, Québec City, Québec, G1R 3S3, Canada.
  2. Endocrinology and Nephrology, CHU de Quebec-Research Center (CHUL), 2705 Boulevard Laurier, Québec City, Québec, G1V 4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, 1050 avenue de la Médecine, Québec City, Québec, G1V 0A6, Canada; Centre de recherche sur le cancer de l'Université Laval, 9, rue McMahon, Québec City, Québec, G1R 3S3, Canada. Electronic address: [email protected].

PMID: 34400276 DOI: 10.1016/j.jsbmb.2021.105963

Abstract

Human 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7), a special multifunctional enzyme, activates the estrogen estrone while inactivating the potent androgen dihydrotestosterone. Thus, this enzyme has become an ideal target for hormone-dependent breast cancer treatment, as its inhibition leads to estradiol reduction and dihydrotestosterone restoration. However, a particular concern has arisen related to an additional role in cholesterol biosynthesis, as inhibition of the enzyme may lead to undesirable side effects. Our findings demonstrate that the available enzyme inhibitors are non-competitive. Among these, many such as INH81, are specific toward sex-hormone conversion, whereas others represented by 4-bromo-ethynylestradiol, are more specific for zymosterone reduction occurring during cholesterol biosynthesis. The binding of non-competitive inhibitors does not affect the substrate binding on the enzyme. This is the first demonstration of non-competitive inhibitors acting selectively on different catalyses, thereby facilitating inhibitor uses for breast cancer treatment. We aim to quickly communicate the novel results.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: Breast cancer; Enzyme catalysis; Enzyme cooperativity; Inhibition; Ligand binding; Multi-specificity; Non-competitive inhibitors

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