| Titre : | Molecular docking studies of small molecules for targeting Estrogen Receptor (ER) |
| Auteurs : | ZINEB SEBAA, Auteur ; Dalal Harkati, Directeur de thèse |
| Type de document : | Mémoire magistere |
| Editeur : | Biskra [Algérie] : Faculté des Sciences Exactes et des Sciences de la Nature et de la Vie, Université Mohamed Khider, 2025 |
| Format : | 1VOL.(43p) / ill.couv.ill.en coul / 30cm |
| Langues: | Anglais |
| Langues originales: | Anglais |
| Mots-clés: | SERDs ; Estrogen receptor alpha ; Breast cancer ; Molecular docking ; Coumarin derivatives ; ADME-T Prediction. |
| Résumé : |
Selective Estrogen Receptor Degraders (SERDs) represent a promising therapeutic strategy for the treatment of estrogen receptor-positive (ER+) breast cancer. This study focuses on the design and evaluation of coumarin-based small molecules as potential oral SERDs using advanced computational approaches. Molecular docking and ADME (Absorption, Distribution, Metabolism, and Excretion) prediction, were employed to assess the physicochemical properties, pharmacokinetics, and safety profiles of selected compounds. Two lead candidates, previously reported in the literature, were further optimized based on their structural and pharmacological features. The compounds were evaluated for their ability to bind and degrade ERα, while maintaining properties suitable for oral administration. The results revealed promising drug-like profiles, including favorable absorption and metabolic stability. This work provides valuable insights into the development of next-generation, orally bioavailable SERDs with improved efficacy and safety, potentially overcoming the limitations of current treatments such as fulvestrant. The findings contribute to the advancement of hormone therapy options for patients with ER+ breast cancer. |
| Sommaire : |
Acknowledgement……………………………………………………………………….….i Abstract ……………………………………………………………………………………ii Résumé …………………………………………………………………………………….iii صخلم………………………………………………………………………………………..iv Contents…………………………………………………………………………………….v List of abbreviations………………………………………………………………...……..vi List of figures …………………………………………………………………………..…ix List of tables……………………………………………………………………………..…xi Genetal Introduction.............1 References ......................3 Chapter I: An overview TOPIC 1: Molecular Modeling I. Molecular Docking ..............3 I.1.Types of molecular docking ....4 I.2.Typical steps in molecular docking ............5 II. In silico assessment of ADME-Toxicity profiling prediction ...........5 1. Absorption ...........6 2. Distribution .........6 3. Metabolism ...........7 4. Excretion ............7 5. Toxicity .............7 TOPIC 2: Estrogen Receptor Alpha In Breast Cancer I. Types of receptors in breast cancer...........10 I.1.Progesterone Receptor (PR)...................10 I.2.Human Epidermal Growth Factor Receptor 2 (HER2) ...........10 I.3.Estrogen Receptor (ER) .......................10 II. Estrogen Receptor alpha (ERα ( ...............11 II.1. Targeted mechanisms for activating ERα .... 11 a) Aromatase inhibitors (AIs) ....................11 b) Selective Estrogen Receptor Modulators (SERMs) ....................11 c) Selective Estrogen Receptor Degraders (SERDs) .....................11 III. Mechanism of action of SERDs in breast cancer treatment .........12 IV. The new treatment for breast cancer ............12 References ...........................14 CHAPTER II: Materials and Methods I. Computer system and web servers..................19 II. Molecular Docking ..............................19 II.1. Preparation of receptor ......................19 II.2 Active site selection .........................20 II.3. Validation of receptor .......................21 II.4. Ligand preparation............................21 II.2.5. Docking execution (Protocol) ...............24 III. In silico study of ADME-Tox properties ........25 III.1.ADME-Toxicity evaluation of coumarin derivatives using ADMETlab 3.0 ..............25 References ............27 CHAPTER III: Results and Discussion I. Molecular docking studies ............................30 II.Evaluation of ADME-Toxicity prediction................38 CONCLUSION .........................41 APPENDIX ...........................43 |
| Type de document : | Mémoire master |
Disponibilité (1)
| Cote | Support | Localisation | Statut |
|---|---|---|---|
| MCH/656 | Mémoire master | bibliothèque sciences exactes | Consultable |
