Several laboratories have demonstrated that activation of drug metabolism by P450s may occur via a mechanism that resembles allosterism from an enzyme kinetic standpoint. Because the effector drug binding site may be located in the same P450 binding pocket where the drug substrate is located, the ability to find and characterize novel effectors (aka heteroactivators) will prove to be important in probing the mechanism of activation. We have used analogues of the prototypical CYP2C9 heteroactivator dapsone to validate a simple docking method that can be used to predict heteroactivators based on ligand binding location in a P450 crystal structure. As proof of concept for the described docking method, a protocol was developed to discover potential heteroactivators from a virtual chemical library through efficient sorting of >40,000 compounds. One of the top-scoring compounds identified was verified to be a CYP2C9 heteroactivator in vitro, and it possessed activity similar to dapsone.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519618 | PMC |
| http://dx.doi.org/10.1021/jm060706p | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A fast and responsive turn-on fluorescent probe based on a quinone conjugated alkoxy derivative for biothiols and a cellular imaging study.
Turk J Chem
November 2024
Division of Organic Chemistry, Department of Chemistry, Faculty of Engineering, İstanbul University-Cerrahpaşa, İstanbul, Turkiye.
The detection of intracellular biothiols (cysteine, N-acetyl cysteine, and glutathione) with high selectivity and sensitivity is important to reveal biological functions. In this study, a 2-(2-methoxy-4-methylphenoxy)-3-chloro-5,8-dihydroxynaphthalene-1,4-dione (DDN-O) compound was newly synthesized and used as a fluorogenic probe (detector molecule) in the fluorometric method for the rapid, highly selective, and sensitive determination of biothiols. The intensity values (λ = 260 nm, λ = 620 nm) of the product were measured by adding biothiols to the reaction medium at varying concentrations and the glutathione equivalent thiol content values of each biothiol were calculated.
View Article and Find Full Text PDFA β-cyclodextrin-based supramolecular photonic crystal hydrogel biosensor with macroporous structures for naked-eye visual detection of cholesterol.
Carbohydr Polym
March 2025
College of Chemistry and Environment, Southwest Minzu University, Chengdu, Sichuan 610225, China; Key Laboratory of Fundamental Chemistry of the State Ethnic Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu, Sichuan 610225, China. Electronic address:
Cholesterol (CHO) is an essential lipid in cell membranes and a precursor for vital living substances. Abnormal CHO levels can cause cardiovascular diseases. Therefore, simple and accurate monitoring of CHO levels is crucial for early diagnosis and effective management of cardiovascular diseases.
View Article and Find Full Text PDFSynthesis of Novel Benzofuran Spiro-2-Pyrrolidine Derivatives via [3+2] Azomethine Ylide Cycloadditions and Their Antitumor Activity.
Int J Mol Sci
December 2024
College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
A synthetic strategy of a three-component spiro-pyrrolidine compound based on benzofuran via an [3+2] azomethine ylide cycloaddition reaction is reported herein. Under mild optimal conditions, this reaction can quickly produce potentially bioactive compounds with a wide range of substrates, high yield, and simple operation. The desired products were obtained with a yield of 74-99% and a diastereomeric ratio (dr) of >20:1.
View Article and Find Full Text PDFLipid nanoparticles (LNP) are the most clinically advanced non-viral gene delivery system. While progress has been made for enhancing delivery, cell specific targeting remains a challenge. Targeting moieties such as antibodies can be chemically-conjugated to LNPs however, this approach is complex and has challenges for scaling up.
View Article and Find Full Text PDFInnovative analytical methodology for skin anti-aging compounds discovery from plant extracts: Integration of High-Performance Thin-Layer Chromatography-in vitro spectrophotometry bioassays with multivariate modeling and molecular docking.
J Chromatogr A
December 2024
Department of Analytical Chemistry, University of Belgrade-Faculty of Chemistry, Studentski trg 12-16, 11158 Belgrade, Serbia. Electronic address:
Skin aging, characterized by reduced elasticity, wrinkles, and changes in pigmentation, presents significant challenges in the cosmetics industry. Identifying compounds that can help mitigate these effects is crucial to developing effective anti-aging treatments and improving skin health. An advanced analytical approach for identifying skin anti-aging compounds within complex natural mixtures must be developed to achieve this.
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!