Ahmed S. Abdelsamie

lab-animal 2023

Potent Dual Inhibitors of Steroid Sulfatase and 17β-Hydroxysteroid Dehydrogenase Type 1 with a Suitable Pharmacokinetic Profile for In Vivo Proof-of-Principle Studies in an Endometriosis Mouse Model

Journal of medicinal chemistry ·doi:10.1021/acs.jmedchem.3c00571

Treating estrogen-dependent diseases like endometriosis with drugs suppressing local estrogen activation may be superior to existing endocrine therapies. Steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) are key…

lab-animal 2022

Dual Targeting of Steroid Sulfatase and 17β-Hydroxysteroid Dehydrogenase Type 1 by a Novel Drug-Prodrug Approach: A Potential Therapeutic Option for the Treatment of Endometriosis

Journal of medicinal chemistry ·doi:10.1021/acs.jmedchem.2c00589

A novel approach for the dual inhibition of steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1(17β HSD1) by a single drug was explored, starting from in-house 17β HSD1 inhibitors via masking their phenolic OH group with a s…

lab-animal 2019

Development of potential preclinical candidates with promising in vitro ADME profile for the inhibition of type 1 and type 2 17β-Hydroxysteroid dehydrogenases: Design, synthesis, and biological evaluation

European Journal of Medicinal Chemistry ·doi:10.1016/j.ejmech.2019.05.084

Estrogens are the major female sex steroid hormones, estradiol (E2) being the most potent form in humans. Disturbing the balance between E2 and its weakly active oxidized form estrone (E1) leads to diverse types of estrogen-dependent diseas…

lab-animal 2017

First Dual Inhibitors of Steroid Sulfatase (STS) and 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1): Designed Multiple Ligands as Novel Potential Therapeutics for Estrogen-Dependent Diseases

Journal of medicinal chemistry ·doi:10.1021/acs.jmedchem.7b00062

STS and 17β-HSD1 are attractive targets for the treatment of estrogen-dependent diseases like endometriosis and breast cancer. The simultaneous inhibition of both enzymes appears more promising than blockage of either protein alone. We desc…

lab-animal 2017

Treatment of estrogen-dependent diseases: Design, synthesis and profiling of a selective 17β-HSD1 inhibitor with sub-nanomolar IC50 for a proof-of-principle study

European Journal of Medicinal Chemistry ·doi:10.1016/j.ejmech.2016.11.004

Current endocrine therapeutics for the estrogen-dependent disease endometriosis often lead to considerable side-effects as they act by reducing estrogen action systemically. A more recent approach takes advantage of the fact that the weak e…

lab-animal 2015

Towards the evaluation in an animal disease model: Fluorinated 17β-HSD1 inhibitors showing strong activity towards both the human and the rat enzyme

European Journal of Medicinal Chemistry ·doi:10.1016/j.ejmech.2015.08.030

17β-Estradiol (E2), the most potent human estrogen, is known to be involved in the etiology of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyses the last ste…

lab-animal 2014

Inhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker

European Journal of Medicinal Chemistry ·doi:10.1016/j.ejmech.2014.05.074

Estradiol is the most potent estrogen in humans. It is known to be involved in the development and proliferation of estrogen dependent diseases such as breast cancer and endometriosis. The last step of its biosynthesis is catalyzed by 17β-h…