Inhibition of isoprenylcysteine carboxyl methyltransferase (Icmt) offers a promising strategy for K-Ras driven cancers. We describe the synthesis and inhibitory activity of substrate-based analogs derived from several novel scaffolds. Modifications of both the prenyl group and thioether of N-acetyl-S-farnesyl-L-cysteine (AFC), a substrate for human Icmt (hIcmt), have resulted in low micromolar inhibitors of Icmt and have given insights into the nature of the prenyl binding site of hIcmt.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037158 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2011.06.053 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comprehensive analysis and validation of TP73 as a biomarker for calcium oxalate nephrolithiasis using machine learning and in vivo and in vitro experiments.
Urolithiasis
November 2024
Department of Urology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Rd, Shanghai, 200040, People's Republic of China.
Calcium oxalate (CaOx) nephrolithiasis constitutes approximately 75% of nephrolithiasis cases, resulting from the supersaturation and deposition of CaOx crystals in renal tissues. Despite their prevalence, precise biomarkers for CaOx nephrolithiasis are lacking. With advances in high-throughput sequencing, we aimed to identify biomarkers of CaOx nephrolithiasis by combining two CaOx nephrolithiasis datasets (GSE73680 and GSE117518).
View Article and Find Full Text PDFestablishes within host cells by inducing anti-apoptotic Bcl-2 family proteins, triggering necrosis, inflammation, and fibrosis. Here, we demonstrate that navitoclax, an orally bioavailable, small-molecule Bcl-2 inhibitor, significantly improves pulmonary tuberculosis (TB) treatments as a host-directed therapy. Addition of navitoclax to standard TB treatments at human equipotent dosing in mouse models of TB, inhibits Bcl-2 expression, leading to improved bacterial clearance, reduced tissue damage / fibrosis and decreased extrapulmonary bacterial dissemination.
View Article and Find Full Text PDFFirst identification of Angiostrongylus spp. in Lissachatina fulica and Cornu aspersum in Antioquia, Colombia.
Biomedica
August 2024
Facultad de Medicina Veterinaria y Zootecnia, Universidad CES, Medellín, Colombia.
Article Synopsis
- Abdominal and neural angiostrongyliasis, caused by Angiostrongylus costaricensis and A. cantonensis, respectively, pose public health risks in Colombia, particularly due to the presence of snail hosts like Lissachatina fulica and Cornu aspersum.
- A study in Antioquia involved collecting and analyzing 5,855 snails to detect Angiostrongylus spp., revealing a 30% prevalence of A. costaricensis, with Medellín having the highest infection rates.
- The results indicate that these snails may be significant intermediate hosts for the parasites, raising concerns for potential human and animal health risks in the region.
Practice determinants for adherence to the Guide for the Comprehensive Clinical Care of Dengue Patients, Urabá (Colombia). A multifaceted approach to implementation research.
PLoS Negl Trop Dis
August 2024
Instituto Colombiano de Medicina Tropical (ICMT- CES), Apartadó, Colombia.
Introduction: Dengue is a significant public health issue in the Urabá region, accounting for 37.5% of morbidity and 41.7% of mortality resulting from dengue in the department of Antioquia (Colombia) in 2018.
View Article and Find Full Text PDFNovel gene fusions in human oropharyngeal carcinoma.
Cancer Genet
August 2024
Division of Translational Oncoimmunology, Aichi Cancer Research Institute, Nagoya, Japan.
Few reports have analyzed the fusion genes involved in carcinogenesis in the oropharynx, where the incidence of human papillomavirus-associated tumors is relatively low. The aim of this study was to identify novel driver fusion genes in patients with oropharyngeal cancer. The study enrolled fifty-seven patients who were diagnosed with oropharyngeal carcinoma.
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!