In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm0310129 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Modulation of Multispecific Transporters by Extract and Its Major Phytoconstituents.
Pharmaceutics
October 2024
Charles River Laboratories Hungary, H-1117 Budapest, Hungary.
One of the major risks associated with the concomitant use of herbal products and therapeutic drugs is herb-drug interactions (HDIs). The most common mechanism leading to HDIs is the inhibition and/or induction of transport proteins and drug-metabolizing enzymes by herbal ingredients, causing changes in the pharmacokinetic disposition of the victim drug. The present study aimed to determine the potential interactions of (UT) (cat's claw), a popular herb due to its supposed health benefits.
View Article and Find Full Text PDFDesign, synthesis and biological evaluation of biaryl amide derivatives as modulators of multi-drug resistance.
Eur J Med Chem
January 2025
School of Pharmacy, Fudan University, Shanghai, 201203, China. Electronic address:
Article Synopsis
- - The study highlights the challenge of multi-drug resistance (MDR) in cancer treatment, mainly due to the overexpression of ABC transporters like P-glycoprotein (P-gp), which affects the effectiveness of chemotherapy drugs.
- - Researchers explored the biaryl amide skeleton for potential agents to reverse MDR and identified a compound, D2, that significantly reversed resistance to drugs like paclitaxel and cisplatin in various cancer cell lines.
- - Compound D2 works by binding to P-gp, lowering its expression, and enhancing drug accumulation in cells, showing promise as a solution to combat MDR in cancer treatments.
Non-essential metals are extremely toxic to living organisms, posing significant health risks, particularly in developing nations where they are a major contributor to illness and death. Although their toxicity is widely acknowledged, the mechanisms by which they are regulated within human cells remain incompletely understood. Specifically, the role of membrane transporters in mediating heavy metal toxicity is not well comprehended.
View Article and Find Full Text PDFNRF2 Modulators of Plant Origin and Their Ability to Overcome Multidrug Resistance in Cancers.
Int J Mol Sci
October 2024
Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Cancer is one of the most common causes of death in the world. Despite the fact that there are many types of therapies available, cancer treatment remains a major challenge. The main reason for the ineffectiveness of chemotherapy is the acquisition of multidrug resistance (MDR) by cancer cells.
View Article and Find Full Text PDFmodels to evaluate multidrug resistance in cancer cells: Biochemical and morphological techniques and pharmacological strategies.
J Toxicol Environ Health B Crit Rev
January 2025
Laboratory of Experimental Cancerology (LabCancer), Department of Biophysics and Physiology, Federal University of Piauí, Teresina, Brazil.
Article Synopsis
- * This review discusses various methodologies for detecting MDR modulators and inhibitors, including bioassays, fluorescent analyses, and molecular testing of resistance proteins.
- * Innovative therapies such as anti-miRNAs, antibody-drug conjugates, and epigenetic modifications are explored as potential solutions to combat MDR and enhance patient outcomes, although no effective anti-MDR therapies currently exist.
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!