View Full Size Research conducted by: Shantanu Roychowdhury (1); Casidy M. Ward (1); Kevin J. Kennedy (1); & Yong Zhao (1) (1) Eurofins Discovery, 6 Research Park Drive, St. Charles, MO 63304 Date of Publication: 2019 Presented at: ISSX 2019 in Portland, OR
Intramolecular [2+2] Photocycloaddition of Altrenogest: Confirmation of Product Structure, Theoretical Mechanistic Insight, and Bioactivity Assessment
ABSTRACT While studying the environmental fate of potent endocrine-active steroid hormones, we observed the formation of an intramolecular [2+2] photocycloaddition product (2) with a novel hexacyclic ring system following photolysis of altrenogest (1). The structure and absolute configuration were established by X-ray diffraction analysis. Theoretical computations identified a barrierless two-step cyclization mechanism for the formationRead More
Nuclear Receptors Regulate Intestinal Inflammation in the Context of IBD
ABSTRACT Gastrointestinal (GI) homeostasis is strongly dependent on nuclear receptor (NR) functions. They play a variety of roles ranging from nutrient uptake, sensing of microbial metabolites, regulation of epithelial intestinal cell integrity to shaping of the intestinal immune cell repertoire. Several NRs are associated with GI pathologies; therefore, systematic analysis of NR biology, the underlyingRead More
Rifamycin SV exhibits strong anti-inflammatory in vitro activity through pregnane X receptor stimulation and NFkB inhibition
ABSTRACTRifamycin SV (rifamycin), is a member of the ansamycin family of antimicrobial compounds which kills bacteria commonly associated with infectious diarrhea and other enteric infections. Rifamycin has been found to be effective in experimental animal models of gut inflammation and its efficacy in these settings has been attributed partially to immunomodulatory non-bactericidal activities. This studyRead More
Sedaxane—Use of Nuclear Receptor Transactivation Assays, Toxicogenomics, and Toxicokinetics as Part of a Mode of Action Framework for Rodent Liver Tumors
ABSTRACT Experimental data demonstrate a mode of action (MOA) for liver tumors in male rats and mice treated with sedaxane that starts with activation of CAR, followed by altered expression of CAR-responsive genes, increased cell proliferation, and eventually clonal expansion of preneoplastic cells, leading to the development of altered foci and tumors. This MOA isRead More
Profiling Drug Activity of Human and Ortholog Xenobiotic-Sensing Receptors: PXR, CAR, AhR, and FXR
View Full Size Research conducted by: Koji Toyokawa (1), Ewa Maddox (1), Jack Vanden Huevel (1,2), & Bruce Sherf (1) (1) INDIGO Biosciences, Inc., 1981 Pine Hall Rd, State College, PA, USA (2) Center for Molecular Toxicology and Carcinogenesis, 325 Life Sciences Building, Penn State University, University Park, PA 16802, USA Date of Publication: 2017
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, hindered by lack of understanding mechanistic information Concern over chemical safety for humans and the environment hasRead More
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 responsible for both ligand recognition and regulation of protein-protein interactions, notably with coregulatory factors. NRs represent important targetsRead More
Cyn Monkey Pregnane X Receptor (cPXR; nr1i2)
INDIGO Offers Next Generation in PXR Assay Systems
Expansion of Assay Critical to the Study of Metabolism and Drug-Drug Interactions State College, PA (June 7, 2016) INDIGO Biosciences, a recognized industry-leading provider of nuclear receptor products and services, announced today that it has completed development of the next generation of Pregnane X Receptor (PXR) technology. Previously available in kits and services for onlyRead More