Potential for layered double hydroxides-based, innovative drug delivery systems.

Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as excellent protection of loaded molecules from undesired degradation. Toxicological studies have also found LDHs to be biocompatible compared with other widely used nanoparticles, such as iron oxide, silica, and single-walled carbon nanotubes.

[Target-specific cytotoxic activity of recombinant fusion toxin C-CPE-ETA' against CLDN-3,4-overexpressing ovarian cancer cells].

Objective: The aim of this study was to explore the possibility of creating a toxin, C-CPE-ETA', by fusing C-terminal high affinity binding domain of CPE (C-CPE) with a truncated form of Pseudomonas aeruginosa exotoxin A (ETA') and to examine whether C-CPE-ETA' could specifically target CLDN-3, 4 molecule and the targeted toxin was cytotoxic against CLDN-3,4-overexpressing ovarian cancer.

Methods: CLDN-3 and CLDN-4 expressions were analyzed at the mRNA level in three ovarian cancer cell lines and epithelial ovarian cancer tissues from 20 patients. After transforming an expression plasmid of C-CPE-ETA' into E.

Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study.

The pregnane X receptor (PXR) plays a critical role in the regulation of human cytochrome P450 3A4 (CYP3A4) gene. In this study, we investigated the effect of an array of compounds isolated from Chinese herbal medicines on the activity of PXR using a luciferase reporter gene assay in transiently transfected HepG2 and Huh7 cells and on the expression of PXR and CYP3A4 in LS174T cells. Furthermore, molecular docking was performed to investigate the binding modes of herbal compounds with PXR.

Herbal interactions with anticancer drugs: mechanistic and clinical considerations.

A large number of herbal remedies (e.g. garlic, mistletoe, Essiac, Lingzhi, and astragalus) are used by cancer patients for treating the cancer and/or reducing the toxicities of chemotherapeutic drugs.

New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I.

CYP2C9 is one of the most abundant CYP enzymes in the human liver ( approximately 20% of hepatic total CYP content). CYP2C9 metabolizes approximately 20% clinical drugs (>120 drugs), including a number of drugs with narrow therapeutic ranges. Some natural compounds are also metabolized, probably leading to the formation of toxic metabolites.

New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part II.

Part I of this article published in the previous issue of Current Drug Metabolism discussed the substrate specificity, inhibitor selectivity and structure-activity relationship (SAR) of human CYP2C9. The features of CYP2C9 pharmacophore and SAR models have been elaborated. Part II of this article will address the homology models of CYP2C9, data from site-directed mutagenesis studies, and crystal structural features of CYP2C9.

Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6.

CYP2B6 is mainly expressed in the liver that has been thought historically to play an insignificant role in human drug metabolism. However, increased interest in this enzyme has been stimulated by the discovery of polymorphic and ethnic differences in CYP2B6 expression, identification of additional substrates for CYP2B6, and evidence for co-regulation with CYP3A4. This paper updates our knowledge about the structure, function, regulation and polymorphism of CYP2B6.

Prediction of deleterious non-synonymous single-nucleotide polymorphisms of human uridine diphosphate glucuronosyltransferase genes.

UDP glucuronosyltransferases (UGTs) are an important class of Phase II enzymes involved in the metabolism and detoxification of numerous xenobiotics including therapeutic drugs and endogenous compounds (e.g. bilirubin).