A high-throughput screen against human DGAT-1 led to the identification of a core structure that was subsequently optimized to afford the potent, selective, and orally bioavailable compound 14. Oral administration at doses ≥0.03 mg/kg significantly reduced postprandial triglycerides in mice following an oral lipid challenge. Further assessment in both acute and chronic safety pharmacology and toxicology studies demonstrated a clean profile up to high plasma levels, thus culminating in the nomination of 14 as clinical candidate ABT-046.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm201524g | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Analysis of the miRNA Transcriptome in and Its Regulation of Diterpenoid Alkaloid Biosynthesis.
Int J Mol Sci
January 2025
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
() is an important medicinal plant in the Aconitum genus that is known for its diterpenoid alkaloids, which exhibit significant pharmacological activity and toxicity, thus making it valuable for both medicinal use and as a biopesticide. Although the biosynthesis of terpenoids is well characterized, the potential gene regulatory role of microRNAs (miRNAs) in terpenoid biosynthesis in remains unclear, and further research is needed to explore this aspect in this species. In this study, miRNA sequencing was conducted to analyze the miRNA population and its targets in .
View Article and Find Full Text PDFA novel panel of peptides with diagnostic potential for serological identification of Borrelia burgdorferi sensu stricto, B. garinii and B. afzelii in human sera.
J Immunol Methods
January 2025
School of Biological Sciences, University of Aberdeen, Scotland, Zoology Building, Tillydrone Avenue, AB24 2TZ Aberdeen, Scotland, United Kingdom.
A novel panel of peptide for serological identification of Borrelia burgdoferi sensu stricto, Borrelia garinii and Borrelia afzelii was developed and assessed in this study. The diagnostic algorithm of the novel test was initially trained testing 10 US human sera including 3 early-stage and 3 late-stage Lyme disease positive sera, 2 sera positive for Babesia and 2 sera positive for Syphilis, all purchased from a private biorepository. Findings were then corroborated testing (a) 33 additional EU follow-up positive sera from seroconverted patients bitten by ticks that tested positive for B.
View Article and Find Full Text PDFThe role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease.
J Cancer Res Ther
December 2024
Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most important methods for treating a wide range of hematologic malignancies and bone marrow failure diseases. However, graft-versus-host disease (GVHD), a major complication associated with this method, can seriously affect the survival and quality of life of patients. Acute GVHD (aGVHD) occurs within 100 days after transplantation, and gastrointestinal aGVHD (GI-aGVHD) is one of the leading causes of nonrecurrent death after allo-HSCT.
View Article and Find Full Text PDFGenome wide landscaping of copy number variations for horse inter-breed variability.
Anim Biotechnol
December 2025
Division of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, India.
Copy number variations (CNVs) have become widely acknowledged as a significant source of genomic variability and phenotypic variance. To understand the genetic variants in horses, CNVs from six Indian horse breeds, Manipuri, Zanskari, Bhutia, Spiti, Kathiawari and Marwari were discovered using Axiom Equine Genotyping Array. These breeds differed in agro-climatic adaptation with distinct phenotypic characters.
View Article and Find Full Text PDFApplying Techniques From Precision Medicine to Predict Challenging Behavior and Inform Clinical Resource Allocation.
Behav Modif
January 2025
West Virginia University, Morgantown, USA.
The identification of behavioral markers that predict the trajectory of behavior could guide the allocation of limited clinical resources to improve efficacy, efficiency, and safety. As a preliminary exploration of this possibility, we conducted a retrospective records review of incident reports for aggression displayed by residents at a secure juvenile detention center. Our purpose was to evaluate latency to first aggression as a candidate behavioral marker for predicting subsequent high-rate aggression.
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!