The orphan nuclear receptor Nur77 has been validated as a potential drug target for treating breast cancer. Therefore, focusing on the SAR study of the lead ( = 354 nM), we found the active compound which exhibited improved Nur77-binding capability ( = 91 nM) and excellent antiproliferative activities against breast cancer cell lines. Interestingly, acted as a potent and selective Nur77 antagonist, displaying good potency against triple-negative breast cancer (TNBC) cell lines but did not inhibit human normal breast cancer cell line MCF-10A (SI > 20). Exceptionally, Nur77-dependently caused mitochondria dysfunction and induced the caspase-dependent apoptosis by mediating the TP53 phosphorylation pathway. Moreover, significantly suppressed MDA-MB-231 xenograft tumor growth but had no apparent side effects in mice and zebrafish. Overall, demonstrated to be the first Nur77 modulator mediating the TP53 phosphorylation pathway that has the potential as a novel anticancer agent for TNBC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.3c01336 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
De-Escalation of Nodal Surgery in Clinically Node-Positive Breast Cancer.
JAMA Surg
January 2025
Breast Unit, Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye.
Importance: Increasing evidence supports the oncologic safety of de-escalating axillary surgery for patients with breast cancer after neoadjuvant chemotherapy (NAC).
Objective: To evaluate the oncologic outcomes of de-escalating axillary surgery among patients with clinically node (cN)-positive breast cancer and patients whose disease became cN negative after NAC (ycN negative).
Design, Setting, And Participants: In the NEOSENTITURK MF-1803 prospective cohort registry trial, patients from 37 centers with cT1-4N1-3M0 disease treated with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) alone or with ypN-negative or ypN-positive disease after NAC were recruited between February 15, 2019, and January 1, 2023, and evaluated.
Double CHEK2 Pathogenic and Low-Risk Variants and Associated Cancer Phenotypes.
JAMA Netw Open
January 2025
Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, Massachusetts.
Importance: CHEK2 pathogenic and likely pathogenic variants (PVs) are common, and low-risk (LR) variants, p.I157T, p.S428F, and p.
View Article and Find Full Text PDFCost-Effectiveness of Breast Cancer Screening Using Digital Mammography in Canada.
JAMA Netw Open
January 2025
Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada.
Importance: Evolving breast cancer treatments have led to improved outcomes but carry a substantial financial burden. The association of treatment costs with the cost-effectiveness of screening mammography is unknown.
Objective: To determine the cost-effectiveness of population-based breast cancer screening in the context of current treatment standards.
Cardiovascular Disease and Breast Cancer Stage at Diagnosis.
JAMA Netw Open
January 2025
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston.
Importance: Cardiovascular disease (CVD) and cancer are the leading causes of mortality in the US. Large-scale population-based and mechanistic studies support a direct effect of CVD on accelerated tumor growth and spread, specifically in breast cancer.
Objective: To assess whether individuals presenting with advanced breast cancers are more likely to have prevalent CVD compared with those with early-stage breast cancers at the time of diagnosis.
Author's Reply to ''Comment on 'Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis''.
Mol Diagn Ther
January 2025
Department of Breast Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Jinghua Road No. 24, Luoyang, 471000, China.
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!