Danazol

Al-Badr, Abdullah A.

doi:10.1016/bs.podrm.2021.10.005

Cited by 3 publications

(1 citation statement)

References 226 publications

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“…CYP3A4 is known to metabolize danazol to the less androgenic 2-hydroxymethylethisterone. Danazol also reportedly inhibits both CYP2C8 and CYP2C9 ( Al-Badr, 2022 ), but this study showed these two enzymes metabolized danazol and impacted its potency as an androgen. Still, no reported CYP2C8 or CYP2C9 metabolite(s) are found in the literature.…”

Section: Discussionmentioning

confidence: 79%

High-throughput AR dimerization assay identifies androgen disrupting chemicals and metabolites

Hallinger

Simmons

2023

Front. Toxicol.

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Introduction: Analysis of streamlined computational models used to predict androgen disrupting chemicals revealed that assays measuring androgen receptor (AR) cofactor recruitment/dimerization were particularly indispensable to high predictivity, especially for AR antagonists. As the original dimerization assays used to develop the minimal assay models are no longer available, new assays must be established and evaluated as suitable alternatives to assess chemicals beyond the original 1,800+ supported by the current data. Here we present the AR2 assay, which is a stable, cell-based method that uses an enzyme complementation approach.Methods: Bipartite domains of the NanoLuc luciferase enzyme were fused to the human AR to quantitatively measure ligand-dependent AR homodimerization. 128 chemicals with known endocrine activity profiles including 43 AR reference chemicals were screened in agonist and antagonist modes and compared to the legacy assays. Test chemicals were rescreened in both modes using a retrofit method to incorporate robust cytochrome P450 (CYP) metabolism to assess CYP-mediated shifts in bioactivity.Results: The AR2 assay is amenable to high-throughput screening with excellent robust Z’-factors (rZ’) for both agonist (0.94) and antagonist (0.85) modes. The AR2 assay successfully classified known agonists (balanced accuracy = 0.92) and antagonists (balanced accuracy = 0.79–0.88) as well as or better than the legacy assays with equal or higher estimated potencies. The subsequent reevaluation of the 128 chemicals tested in the presence of individual human CYP enzymes changed the activity calls for five compounds and shifted the estimated potencies for several others.Discussion: This study shows the AR2 assay is well suited to replace the previous AR dimerization assays in a revised computational model to predict AR bioactivity for parent chemicals and their metabolites.

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Section: Discussionmentioning

confidence: 79%

High-throughput AR dimerization assay identifies androgen disrupting chemicals and metabolites

Hallinger

Simmons

2023

Front. Toxicol.

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Isoxazole compounds: Unveiling the synthetic strategy, in-silico SAR & toxicity studies and future perspective as PARP inhibitor in cancer therapy

Malik,

Pal

2024

European Journal of Medicinal Chemistry

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Effectiveness of Hormonal Treatment in Patients With Combined Endometrial Pathology and Benign Formations of Mammary Glands

Shapoval

2022

Modern Medical Technology

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Issues related to the treatment of HPE are still very relevant, which is due to the high frequency of relapses of this disease. Today, in the arsenal of modern medicine, there are various approaches to the treatment of HPE. However, the development of benign neoplasms of the mammary glands against the background of HPE limits the possibilities of conservative treatment. Hormonal therapy remains one of the most common methods of treating HPE. The purpose of the study: to optimize the treatment of patients with various types of hyperplastic processes of the endometrium in combination with benign diseases of the mammary glands. Materials and methods. A prospective study of 90 women aged 18 to 47 was conducted. The main group consisted of patients who were diagnosed with HPE and benign diseases of the mammary glands. The comparison group included patients who were diagnosed with HPE without accompanying pathology of the mammary glands. For the treatment of endometrial hyperplasia without atypia, medroxyprogesterone was used, for the treatment of atypical endometrial hyperplasia, medroxyprogesterone was used in combination with a gonadotropin-releasing hormone analog. For the treatment of patients with combined pathology, the commercial drug Danazol or medroxyprogesterone in combination with Koberlin was used. The results. The implementation of various treatment regimens for patients with HPE and benign breast neoplasms showed that the more effective treatment regimen was the one involving the use of Danazol. In this group of patients, the levels of estradiol and progesterone in the blood plasma normalized already after six months of using the drug. Conclusion. The study of the levels of estrogens, progestins and gonadotropic hormones showed that in the patients of the comparison group, the best treatment scheme is the combined use of medroxyprogesterone and gonadotropin-releasing hormone analogues compared to the monouse of only medroxyprogesterone. In patients with the combined pathology of HPE and mastopathy, the best treatment scheme is the use of Danazol.

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Danazol

Cited by 3 publications

References 226 publications

High-throughput AR dimerization assay identifies androgen disrupting chemicals and metabolites

High-throughput AR dimerization assay identifies androgen disrupting chemicals and metabolites

Isoxazole compounds: Unveiling the synthetic strategy, in-silico SAR & toxicity studies and future perspective as PARP inhibitor in cancer therapy

Effectiveness of Hormonal Treatment in Patients With Combined Endometrial Pathology and Benign Formations of Mammary Glands

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