Insertion of 3 to 4 mutations, based on in silico modelling, in a diverse set of natural miniproteins generates potent androgen receptor (AR) binders and a clear insight into the structure-activity relationship of such coactivator mimics concerning helix length.

Download full-text PDF

Source
http://dx.doi.org/10.1039/b910677dDOI Listing

Publication Analysis

Top Keywords

androgen receptor
8
coactivator mimics
8
computational design
4
design synthesis
4
synthesis evaluation
4
evaluation miniproteins
4
miniproteins androgen
4
receptor coactivator
4
mimics insertion
4
insertion mutations
4

Similar Publications

Occurrence, Bioaccumulation, and Human Exposure Risk of the Antiandrogenic Fluorescent Dye 7-(Dimethylamino)-4-methylcoumarin and 7-(Diethylamino)-4-methylcoumarin in the Dongjiang River Basin, South China.

Toxics

December 2024

Key Laboratory of Ministry of Education for Water Quality Security and Protection in Pearl River Delta, School of Environmental Science and Engineering, Guangzhou University, Guangzhou 510006, China.

Recently, 7-diethylamino-4-methylcoumarin (DEAMC) has been identified as a potent antiandrogenic compound in the surface water; however, little is known about the antiandrogenic potentials of other synthetic coumarins and their occurrence in the aquatic ecosystem. In this study, for the first time, we observed that 7-dimethylamino-4-methylcoumarin (DAMC) elicited androgen receptor (AR) antagonistic activity with a 50% inhibitory concentration (IC) of 1.46 µM, which is 14.

View Article and Find Full Text PDF

Prostate cancer remains a significant global health concern, prompting ongoing exploration of novel therapeutic agents. Licochalcone A, a natural product in the chalcone family isolated from licorice root, is characterized by its enone structure and demonstrates antiproliferative activity in the micromolar range across various cell lines, including prostate cancer. Building on our prior success in enhancing curcumin's antiproliferative potency by replacing the substituted phenol with a 1-alkyl-1H-imizadol-2-yl moiety, we applied a similar approach to design a new class of licochalcone A-inspired chalcones.

View Article and Find Full Text PDF

Androgen receptor (AR)-negative triple-negative breast cancer (TNBC), often termed quadruple-negative breast cancer (QNBC), disproportionately impacts women of African descent, leading to poorer overall survival (OS). MiRNAs regulate the expression of gene drivers involved in critical signaling pathways in TNBC, such as the gene, and their expression varies across races and breast cancer subtypes. This study investigates whether differentially expressed miRNAs influence AR transcription, potentially contributing to the observed disparities between African American (AA) and European American (EA) QNBC patients.

View Article and Find Full Text PDF

Despite treatment, prostate cancer commonly progresses into castration-resistant prostate cancer (CRPC), which remains largely incurable, requiring the development of new interventions. Darolutamide is an orally administered second-generation androgen receptor inhibitor indicated for patients with non-metastatic CRPC or metastatic hormone-sensitive prostate cancer. Here, we evaluated the effect of androgen receptor (AR) inhibition by darolutamide in combination with DNA double-strand-break-inducing targeted radium-223 alpha therapy in vitro and in an intratibial LNCaP xenograft model mimicking prostate cancer metastasized to bone.

View Article and Find Full Text PDF

This study investigated the influence of two in vitro fertilization (IVF) protocols-controlled ovarian hyperstimulation (COH) and a modified natural cycle protocol-on gene expression levels (Anti-Müllerian Hormone (), Anti-Müllerian Hormone Receptor Type 2 (), Follicle-Stimulating Hormone Receptor (), and Androgen Receptor ()) and the subsequent reproductive outcomes of assisted reproductive technology (ART). Gene expression, as well as oocyte, zygote, and embryo morphological parameters, were analyzed to evaluate the differences between the protocols. Our findings show that expression was significantly associated with successful fertilization, while expression correlated with improved embryo transfer outcomes.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!