In silico comparison between the mutated and wild-type androgen receptors and their influence on the selection of optimum androgenic receptor blockers for the treatment of prostate cancer
Abstract
Background: Prostate cancer is a disease that occurs in men aged more than 50 years. In Iraq, 8.89 men per 100,000 population suffer from prostate cancer, with the incidence being 14,016 cases and mortality being 6,367 cases. Despite advances in treatment against prostate cancer, it can become resistant to drugs. Therefore, the aim of current study was to search and identify binding sites for the repositioning of drugs by computational methods (docking). Methods: Based on the protein structure of the wild androgen receptor, the analysis parameters (22x22x22 on the X, Y, and Z axes) were established. Results: The interactions of the natural ligands with androgen receptor were 10.0 (testosterone) and 10.8 (dihydrotestosterone) while mutated androgen receptor (T877A) had a low affinity with testosterone and dihydrotestosterone (-5.3 and -6.7, respectively). In the interactions of both receptors with the reported inhibitors (antagonists), a decrease with Bicalutamide (-8.3 and -4.3, respectively) and an increase in affinity with Flutamide and Nilutamide (-7.7 and 8.6, wild AR; -8.7 and -9.3 AR T877A) were observed. As for Enzalutamide and Apalutamide (second-generation antagonists), the change was minimal between wild androgen receptor and T877A (-7.6 and -7.7; -7.3 and -7.3, respectively). The change in the affinity of the ligands with androgen receptor and androgen receptor T877A shows how a mutation alters the bonds between these molecules. Conclusion: The identification of…
Read the paper
Related studies
- Induced osteoblast differentiation by amide derivatives of stilbene: The possible osteogenic agents
- On model selections for repeated measurement data in clinical studies
- Regulation of GLUT transporters by flavonoids in androgen-sensitive and -insensitive prostate cancer cells
- Region-specific microRNA signatures in the human epididymis
- Synthesis, biological evaluation and molecular docking of 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs containing the piperazine moiety
- In Vitro characterization of the endocrine disrupting effects of per- and poly-fluoroalkyl substances (PFASs) on the human androgen receptor
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.