Nestorone® (NES) a Novel Progestin for Non-oral Contraception: Structure-activity Relationships and Brain Metabolism Studies
ABSTRACT Nestorone® (NES) is a highly potent non-androgenic progestin being developed for contraception. NES is a synthetic progestin that may possess neuroprotective and myelin regenerative potential as an added health benefits. In receptor transactivation...
Differential modulation of FXR activity by chlorophacinone and ivermectin analogs
ABSTRACT Chemicals that alter normal function of farnesoid X receptor (FXR) have been shown to affect the homeostasis of bile acids, glucose, and lipids. Several structural classes of environmental chemicals and drugs that modulated FXR transactivation were previously...
Mouse Liver Tumor Mode of Action: Use of Toxicogenomics in Weight of Evidence for Human Relevance Assessment
ABSTRACT The Use of Toxicogenomics in Chemical Safety Testing Current safety testing is geared to produce and accept descriptive data from high-dose animal studies Interpretation of this information has effectively protected our health and safety for decates; however,...
Nuclear Receptors and Control of Drug Metabolism
The metabolism of lipophilic xenobiotics, including drugs and nutrients, involves a coordinated process of biotransformation and transport, ultimately aimed at detoxifying and eliminating potentially harmful compounds. Most of the tissues and organs are well...
Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney
ABSTRACT Background Excess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1...
Novel synthesised flavone derivatives provide significant insight into the structural features required for enhanced anti-proliferative activity
ABSTRACT With many cancers showing resistance to current chemotherapies, the search for novel anti-cancer agents is attracting considerable attention. Natural flavonoids have been identified as useful leads in such programmes. However, since an in-depth understanding...
Effects of Munitions Compounds on Xenobiotic-Activated Nuclear Receptors and Signaling Pathways
ABSTRACT Exposure to certain munitions compounds is know to alter physiological functions in test organisms, however little is known about their molecular and cellular effects. Several nuclear receptors are regulated by xenobiotic compounds. These nuclear receptors...
Identification of a Chrysanthemic Ester as an Apolipoprotein E Inducer in Astrocytes
ABSTRACT The apolipoprotein E (APOE) gene is the most highly associated susceptibility locus for late onset Alzheimer’s Disease (AD), and augmenting the beneficial physiological functions of apoE is a proposed therapeutic strategy. In a high throughput phenotypic...
Leoligin, the major lignan from edelweiss, inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase and reduces cholesterol levels in ApoE −/− mice
ABSTRACT The health benefit through the control of lipid levels in hyperlipidaemic individuals is evident from a large number of studies. The pharmacological options to achieve this goal shall be as specific and personalized as the reasons for and co-factors of...
Species Differences in Pregnane X Receptor Activation: Examination of common laboratory animal species
ABSTRACT Nuclear receptors (NRs) are ligand-dependent transcription factors found in many species that regulate the expression of important target genes involved in a spectrum of developmental and physiological processes. The ligand binding domain (LBD) of NRs is...