Inhibition of human placental aromatase in a perfusion model. Comparison with kinetic, cell-free experiments

Klein, H.; Bartsch, W.; Niemand, A.; Stürenburg, Hans-Jörg; Voigt, K. D.

doi:10.1016/0022-4731(88)90261-0

Cited by 6 publications

(2 citation statements)

References 26 publications

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“…Theoretically, their duration of action in vivo should be prolonged and related primarily to the rate at which new enzyme can be synthesized. These concepts require experimental verification (194). Specificity of inhibition as well as intrinsic biological activity are important considerations regarding aromatase inhibitors (193).…”

Section: E Development Of Improved Aromatase Inhibitorsmentioning

confidence: 99%

Endocrine Treatment of Breast Cancer in Women

Santen¹,

Manni²,

Harvey³

et al. 1990

Endocrine Reviews

380

157

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Section: E Development Of Improved Aromatase Inhibitorsmentioning

confidence: 99%

Endocrine Treatment of Breast Cancer in Women

Santen¹,

Manni²,

Harvey³

et al. 1990

Endocrine Reviews

380

157

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“…They have concluded that the tested aromatase inhibitors redirect the third oxidation step with the covalent bonding of the steroid to the enzyme, which results in irreversible enzyme inactivation, while the 3keto-4-ene system, also present in testolactone, displays a kinetic profile expected for a suicide substrate. This assumption about the irreversible inhibition of aromatase was further studied by Klein et al [44] in their research on the perfusion of the human placenta, and the results were compared with those from kinetic experiments in a cell-free system. They have concluded that examined inhibitors (1-methylandrost-1,4-diene-3,17-dione; 19-azidoandrost-4-ene-3,17-dione; 4-hydroxyandrost-4-ene-3,17-dione; and testolactone) caused irreversible aromatase inactivation in a cell-free system, but this phenomenon could not be observed during the perfusion experiments.…”

Section: Medicinal Uses Benefits and Side Effects Of Testolactonementioning

confidence: 99%

Testolactone: The Rise and Fall of a Drug

Savić

Kuzminac

Nikolić

2023

DDC

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Testolactone is structurally related to testosterone and belongs to the first generation of aromatase inhibitors. It is a non-selective irreversible aromatase enzyme inhibitor that was one of the first steroids used in the clinical treatment of breast cancer. The use of testolactone in the treatment of breast cancer started in 1970, although its ability to inhibit aromatase was not discovered until 1975. Its use was primarily based on the inhibition of estrogen synthesis, which was applied in the treatment of estrogen-dependent breast cancers, in the treatment of disorders of sex steroid excess, familial male-limited precocious puberty, or in the treatment of patients with McCune–Albright syndrome, etc. The weak inhibitory activity of testolactone, and the moderate clinical response, prevented its widespread use, which ultimately resulted in withdrawal from the drug market in 2008. This review paper is dedicated to testolactone, its rise in the second half of the 20th century, and its fall in the first decade of the 21st century. Regardless of withdrawal from the market, for many years testolactone was a drug that improved the quality of life of patients facing one of the most serious diseases today, and for this reason, this paper describes medicinal application, synthesis, and modifications of testolactone.

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