A simple CE assay for the rapid determination of the in vitro metabolic stability of verapamil in human liver microsomes has been developed and validated. Verapamil was used as the prototype drug since it is extensively metabolized in human liver microsomes. The assay showed good intra- (CV < or = 10%) and interday (CV < or = 8%) reproducibility. The recovery of verapamil after incubation at 37 degrees C for 60 min with human liver microsomes was low (15 +/- 1%) and two metabolites were detected. The method is currently in use for assessing the metabolic stability of new drug candidates at an early stage of lead optimization at Cardiome Pharma Corp. (Vancouver, BC, Canada).
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Integrated single-cell RNA sequencing reveals the tumor heterogeneity and microenvironment landscape during liver metastasis in adenocarcinoma of esophagogastric junction.
Front Immunol
January 2025
Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Background: Adenocarcinoma of the esophagogastric junction (AEGJ) is a highly aggressive tumor that frequently metastasizes to the liver. Understanding the cellular and molecular mechanisms that drive this process is essential for developing effective therapies.
Methods: We employed single-cell RNA sequencing to analyze the tumor heterogeneity and microenvironmental landscape in patients with AEGJ liver metastases.
Immunotherapy combined with chemotherapy without locoregional radiotherapy in metastatic nasopharyngeal carcinoma: two case reports and a literature review.
Front Immunol
January 2025
Department of Otolaryngology, Changhai Hospital, Naval Medical University, Shanghai, China.
Background: There is no consensus regarding the optimal regimen for metastatic nasopharyngeal carcinoma (dmNPC). Locoregional intensity modulated radiotherapy (LRRT) following palliative chemotherapy (PCT) has been shown to prolong the overall survival (OS) and improve the progression-free survival (PFS) of patients with dmNPC, compared with PCT alone. However, patients with a high tumor burden do not benefit from additional LRRT, which inevitably results in toxicity.
View Article and Find Full Text PDFThe role and therapeutic targeting of the CCL2/CCR2 signaling axis in inflammatory and fibrotic diseases.
Front Immunol
January 2025
Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.
CCL2, a pivotal cytokine within the chemokine family, functions by binding to its receptor CCR2. The CCL2/CCR2 signaling pathway plays a crucial role in the development of fibrosis across multiple organ systems by modulating the recruitment and activation of immune cells, which in turn influences the progression of fibrotic diseases in the liver, intestines, pancreas, heart, lungs, kidneys, and other organs. This paper introduces the biological functions of CCL2 and CCR2, highlighting their similarities and differences concerning fibrotic disorders in various organ systems, and reviews recent progress in the diagnosis and treatment of clinical fibrotic diseases linked to the CCL2/CCR2 signaling pathway.
View Article and Find Full Text PDFIntegrated single-cell and bulk transcriptome analysis of R-loop score-based signature with regard to immune microenvironment, lipid metabolism and prognosis in HCC.
Front Immunol
January 2025
National Key Laboratory of Draggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Background: Hepatocellular carcinoma (HCC) is one of the most prevalent causes of cancer-related morbidity and mortality worldwide. Late-stage detection and the complex molecular mechanisms driving tumor progression contribute significantly to its poor prognosis. Dysregulated R-loops, three-stranded nucleic acid structures associated with genome instability, play a key role in the malignant characteristics of various tumors.
View Article and Find Full Text PDFOrganoids and spheroids: advanced models for liver cancer research.
Front Cell Dev Biol
January 2025
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Liver cancer is a leading cause of cancer-related deaths worldwide, highlighting the need for innovative approaches to understand its complex biology and develop effective treatments. While traditional animal models have played a vital role in liver cancer research, ethical concerns and the demand for more human-relevant systems have driven the development of advanced models. Spheroids and organoids have emerged as powerful tools due to their ability to replicate tumor microenvironment and facilitate preclinical drug development.
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!