New Publications
Scientific studies, scholarly articles, and patent information to Nuclear Receptors and Nuclear Receptor research.
Synthesis and evaluation of 4-cycloheptylphenols as selective Estrogen receptor-β agonists (SERBAs)
ABSTRACT A short and efficient route to 4-(4-hydroxyphenyl)cycloheptanemethanol was developed, which resulted in the preparation of a mixture of 4 stereoisomers. The stereoisomers were separated by preparative HPLC, and two of the stereoisomers identified by X-ray crystallography. The stereoisomers, as well as a small family of 4-cycloheptylphenol derivatives, were evaluated as estrogen receptor-beta agonists. The lead compound, 4-(4-hydroxyphenyl)cycloheptanemethanol was selective for activatingRead More
Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination
ABSTRACT Regeneration of myelin is mediated by oligodendrocyte progenitor cells—an abundant stem cell population in the central nervous system (CNS) and the principal source of new myelinating oligodendrocytes. Loss of myelin-producing oligodendrocytes in the CNS underlies a number of neurological diseases, including multiple sclerosis and diverse genetic diseases. High-throughput chemical screening approaches have been usedRead More
Involvement of estrogen receptor α in pro-pruritic and pro-inflammatory responses in a mouse model of allergic dermatitis
ABSTRACT It has been reported that endogenous or exogenous estrogens can affect the immune system, resulting in immune disorders; however, their direct involvement in such conditions remains to be demonstrated. The purpose of this study was to investigate whether estrogen receptors (ER) are directly implicated in pro-pruritic and pro-inflammatory reactions in cutaneous allergy. Initially, enhancement of the pro-inflammatoryRead More
Comparative Evaluation of Gemcabene and Peroxisome Proliferator–Activated Receptor Ligands in Transcriptional Assays of Peroxisome Proliferator–Activated Receptors: Implication for the Treatment of Hyperlipidemia and Cardiovascular Disease
ABSTRACT Gemcabene, a late-stage clinical candidate, has shown efficacy for LDL-C, non-HDL cholesterol, apoB, triglycerides, and hsCRP reduction, all risk factors for cardiovascular disease. In rodents, gemcabene showed changes in targets, including apoC-III, apoA-I, peroxisomal enzymes, considered regulated through peroxisome proliferator–activated receptor (PPAR) gene activation, suggesting a PPAR-mediated mechanism of action for the observed hypolipidemic effects observedRead More
1α,25-dihydroxyvitamin D3-eluting nanofibrous dressings induce endogenous antimicrobial peptide expression
ABSTRACT Aim: The aim of this study was to develop a nanofiber-based dressing capable of local sustained delivery of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and augmenting human CAMP induction. Materials & methods:Nanofibrous wound dressings containing 1,25(OH)2D3 were successfully prepared by electrospinning, which were examined in vitro, in vivo and ex vivo. Results: 1,25(OH)2D3 was successfully loaded into nanofibers with encapsulation efficiency larger than 90%. 1,25(OH)2D3 showed a sustained release from nanofibersRead More
Discovery of Retinoic Acid-Related Orphan Receptor γt Inverse Agonists via Docking and Negative Image-Based Screening
ABSTRACT Retinoic acid-related orphan receptor γt (RORγt) has a vital role in the differentiation of T-helper 17 (TH17) cells. Potent and specific RORγt inverse agonists are sought for treating TH17-related diseases such as psoriasis, rheumatoid arthritis, and type 1 diabetes. Here, the aim was to discover novel RORγt ligands using both standard molecular docking andRead More
Bitter melon seed oil increases mitochondrial content in gastrocnemius muscle and improves running endurance in sedentary C57BL/6 J mice
ABSTRACT The α-eleostearic acid (α-ESA) in bitter melon seed oil (BMSO) is efficiently converted by the body into rumenic acid. The objective of this study was to investigate effects of BMSO on skeletal muscle fiber-type switch and endurance capacity in mice, with or without exercise training. In a 3 x 2 factorial design, C57BL/6 JRead More
A-C Estrogens as Potent and Selective Estrogen Receptor-Beta Agonists (SERBAs) to Enhance Memory Consolidation under Low-Estrogen Conditions
ABSTRACT Estrogen receptor-beta (ERβ) is a drug target for memory consolidation in postmenopausal women. Herein is reported a series of potent and selective ERβ agonists (SERBAs) with in vivo efficacy that are A–C estrogens, lacking the B and D estrogen rings. The most potent and selective A–C estrogen is selective for activating ER relative toRead More
Structure-guided evolution of a 2-phenyl-4-carboxyquinoline chemotype into PPARα selective agonists: New leads for oculovascular conditions
ABSTRACT Small molecule agonism of PPARα represents a promising new avenue for the development of non-invasive treatments for oculovascular diseases like diabetic retinopathy and age-related macular degeneration. Herein we report initial structure–activity relationships for the newly identified quinoline-based PPARα agonist, Y-0452. Preliminary computational studies led to the hypothesis that carboxylic acid transposition and deconstruction ofRead More
Pyrazolone Compounds and Uses Thereof: Patent Application
ABSTRACT The invention disclosed herein is directed to compounds of Formula I and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, acute or chronic myeloid leukemia, melanoma, and other cancers. The invention also includes pharmaceutical compositions comprising a therapeutically effective amount of compound ofRead More