The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway induces apoptosis in cancer cells but not in normal cells. Therefore, this pathway has attracted attention regarding possible clinical treatment of cancer. However, many cancer cells demonstrate TRAIL resistance. To overcome this problem, small molecules that sensitize cancer cells to TRAIL are desired. Heterocyclic derivatives of the natural product, fuligocandin B (2), with activity for overcoming TRAIL resistance were synthesized, and their activity was evaluated. Of the synthetic molecules, the quinoline derivative (10g) showed potent activity against TRAIL-resistant gastric adenocarcinoma cells. After a docking study of the target protein valosin-containing protein, 7'-amino fuligocandin B (10m) was designed and synthesized. Compound 10m also showed good activity for overcoming TRAIL resistance. 10m produced a 49.7% difference in viability with TRAIL at 30 µM compared to without TRAIL. This activity was better than that of fuligocandin B (2).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1248/cpb.c18-00308 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The effect of gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review and network meta-analysis.
Front Nutr
January 2025
Department of Spleen, Stomach, Hepatobiliary Disease, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Background: The incidence of NAFLD is increasing. Preclinical evidences indicate that modulation of the gut microbiome could be a promising target in nonalcoholic fatty liver disease.
Method: A systematic review and network meta-analysis was conducted to compare the effect of probiotics, synbiotics, prebiotics, fecal microbiota transplant, and antibiotics on the liver-enzyme, metabolic effects and liver-specific in patients with NAFLD.
The effect of a walking, dancing, and strength training program on the functional fitness of adults with intellectual disability: A randomised controlled trial.
J Intellect Dev Disabil
June 2024
Department of Human Movement Science, Cape Peninsula University of Technology, Wellington, South Africa.
Background: Many adults with intellectual disabilities live a sedentary lifestyle, have low levels of functional fitness and are overweight. The purpose of this study was to determine whether an exercise intervention with activities which are simple, fun, accessible and adapted for socialising in a group would elicit significant improvements in various parameters associated with functional fitness for adults with intellectual disabilities.
Methods: Forty-two adults with intellectual disability (44.
Synergistic combination therapy with ONC201 or ONC206, and enzalutamide or darolutamide in preclinical studies of castration-resistant prostate cancer.
Am J Cancer Res
December 2024
Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University Providence, RI 02903, USA.
Androgen receptor (AR) signaling is a target in prostate cancer therapy and can be treated with non-steroidal anti-androgens (NSAA) including enzalutamide, and apalutamide for patients with advanced disease. Metastatic castration-resistant prostate cancer (mCPRC) develop resistance becomes refractory to therapy limiting patient overall survival. Darolutamide is a novel next-generation androgen receptor-signaling inhibitor that is FDA approved for non-metastatic castration resistant prostate cancer (nmCRPC).
View Article and Find Full Text PDFEnterprise internal audit data encryption based on blockchain technology.
PLoS One
January 2025
Taiyuan University, Taiyuan, China.
Internal auditing demands innovative and secure solutions in today's business environment, with increasing competitive pressure and frequent occurrences of risky and illegal behaviours. Blockchain along with secure databases like encryption improves internal audit security through immutability and transparency. Hence integrating blockchain with homomorphic encryption and multi-factor authentication improves privacy and mitigates computational overhead.
View Article and Find Full Text PDFDivergent roles of mA in orchestrating brown and white adipocyte transcriptomes and systemic metabolism.
Nat Commun
January 2025
Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center; Department of Medicine, BIDMC; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
N-methyladenosine (mA) is among the most abundant mRNA modifications, yet its cell-type-specific regulatory roles remain unclear. Here we show that mA methyltransferase-like 14 (METTL14) differentially regulates transcriptome in brown versus white adipose tissue (BAT and WAT), leading to divergent metabolic outcomes. In humans and mice with insulin resistance, METTL14 expression differs significantly from BAT and WAT in the context of its correlation with insulin sensitivity.
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!