A series of ER-PROTACs compounds were designed, synthesized and tested for their ability to degrade estrogen receptor proteins and exhibit Human breast cancer cells (MCF-7) inhibition activity. Molecular docking simulations were performed using Discovery studio. Among these compounds, QDE-003-W had the highest estrogen receptor protein degradation ability and cellular activity, with a DC value of 95 nM, for estrogen receptor protein degradation and an IC value of 30.2 nM for cellular activity. Furthermore, the molecular docking study revealed that the biological activity of QDE-003-W depended on its suitable linker length, which gave us some reference significance for the study of ER-PROTACs. And compared with fulvestrant, QDE-003-W exhibited more favorable pharmacokinetic (PK) characteristics. No significant adverse side effects were observed under the administration protocol, which indicates that the tested mice had excellent tolerance to both the administration method and the dosage. Such favorable PK characteristics and safety features further enhance the prospects of QDE-003-W as a viable candidate for subsequent preclinical and clinical development.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2025.118111 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Post-marketing safety of elacestrant in breast cancer: a pharmacovigilance investigation using the FDA adverse event reporting system.
BMC Pharmacol Toxicol
March 2025
Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030032, China.
Background: Recently, the US Food and Drug Administration approved a new oral selective estrogen receptor downregulator for breast cancer, namely, elacestrant (Orserdu). This study aimed to analyze the signals of adverse events (AEs) within the introduction of elacestrant to the market using the FDA Adverse Event Reporting System (FAERS) database.
Methods: Reports on the AEs of elacestrant after its marketing were obtained from the FAERS database.
Genome-wide mapping and quantification of DNA damage induced by catechol estrogens using Click-Probe-Seq and LC-MS.
Commun Biol
March 2025
Department of Chemistry, National Cheng Kung University, Tainan, Taiwan.
Genotoxic estrogen metabolites generate various DNA lesions; however, their target genes and carcinogenic mechanisms remain unexplored. Here, genome-wide sequencing using click probe enrichment coupled with liquid chromatography-tandem mass spectrometry (Click-Probe-Seq/LC-MS) is developed to identify damaged genes and characterize the released and stable adducts induced by 4-hydroxy-17β-estradiol (4OHE2) in MCF-7 cell chromatin. The data reveal that guanine nucleobases in the GC-rich transcription-relevant domain are the main target sites.
View Article and Find Full Text PDFVaginal microbiota transplantation alleviates vaginal atrophy in ovariectomized mice.
Sci Rep
March 2025
The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, P. R. China.
Vaginal atrophy is a prevalent symptom in menopausal women, affecting over 50% of older women and patients with loss of ovarian function. The role of factors other than estrogen, such as the vaginal microbiota (VM), in the development of vaginal atrophy has not been fully explored. Therefore, we selected 8-week-old C57 mice with bilateral ovariectomy for experimentation.
View Article and Find Full Text PDFEstradiol protects against pain-facilitated fentanyl use via suppression of opioid-evoked dopamine activity in males.
Neuron
March 2025
Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA; Pain Center, Washington University in St. Louis, St. Louis, MO, USA; School of Medicine, Washington University in St. Louis, St. Louis, MO, USA; Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, USA; Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA. Electronic address:
Pain relief is the most frequently reported motivation for opioid misuse, but it remains unclear how pain alters reward pathway function contributing to maladaptive opioid use and whether these neuroadaptations occur in a sex-specific manner. Here, we show that persistent inflammatory pain leads to augmented fentanyl self-administration in male, not female, rats. Wireless in vivo fiber photometry recordings and chemogenetic manipulations indicate that pain-facilitated fentanyl use is mediated by enhanced ventral tegmental area dopamine (VTA) neuron responses during self-administration.
View Article and Find Full Text PDFDesign, synthesis, and biological evaluation of novel PROTACs compounds with good ERα degradation ability.
Bioorg Med Chem
February 2025
Department of Natural Product Chemistry, Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China. Electronic address:
A series of ER-PROTACs compounds were designed, synthesized and tested for their ability to degrade estrogen receptor proteins and exhibit Human breast cancer cells (MCF-7) inhibition activity. Molecular docking simulations were performed using Discovery studio. Among these compounds, QDE-003-W had the highest estrogen receptor protein degradation ability and cellular activity, with a DC value of 95 nM, for estrogen receptor protein degradation and an IC value of 30.
View Article and Find Full Text PDFWant 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!