Abstract Withanolide derivatives have anticancer, anti-inflammatory, and other functions and are components of Indian traditional Ayurvedic medicine. Here, we found that 2,3-dihydro-3β-methoxy withaferin-A (3βmWi-A), a derivative of withaferin-A (Wi-A) belonging to a class of withanolides that are abundant in Ashwagandha (Withania somnifera), lengthened the period of the circadian clock. This compound dose-dependently elongated circadian rhythmsRead More
Metadichol, A Novel ROR Gamma Inverse Agonist and Its Applications in Psoriasis
ABSTRACT Psoriasis affects 3% of the population worldwide, and there is no known cure. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, and Crohn’s disease. Psoriasis treatments today include steroid and vitamin D3 cream, ultraviolet light, and immune system suppressing medications such as methotrexate. The T cells responsible for psoriasisRead More
ROR Modulators and Their Uses
ABSTRACT There are high unmet medical needs in the few established therapies for several autoimmune, inflammatory and metabolic diseases. Despite the diverse clinical manifestations of these diseases, Retinoic Acid Receptor-Related Orphan Receptors (RORs) regulate and contribute to the pathogenesis of these diseases through modulation of immune responses and lipid/glucose homeostasis. Only recently has the criticalRead More
In vivo regulation of gene expression and T helper type 17 differentiation by RORγt inverse agonists
ABSTRACT The orphan nuclear receptor, retinoic acid receptor-related orphan nuclear receptor γt (RORγt), is required for the development and pathogenic function of interleukin-17A-secreting CD4+ T helper type 17 (Th17) cells. Whereas small molecule RORγt antagonists impair Th17 cell development and attenuate autoimmune inflammation in vivo, the broader effects of these inhibitors on RORγt-dependent gene expressionRead More
Oxysterols are agonist ligands of RORγt and drive Th17 cell differentiation
ABSTRACT The RAR-related orphan receptor gamma t (RORγt) is a nuclear receptor required for generating IL-17–producing CD4+ Th17 T cells, which are essential in host defense and may play key pathogenic roles in autoimmune diseases. Oxysterols elicit profound effects on immune and inflammatory responses as well as on cholesterol and lipid metabolism. Here, we describe the identification of several naturally occurringRead More
Examination of Retinoid-like Compounds for Human RXRs, RARs, and RORs
View Full Size Research conducted by: Prajakta Albrecht (1), Koji Toyokawa (1), Ewa Maddox (1), Palmer Cramer (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,Read More
Examination of Specificity of Retinoid-like Compounds for Human RXRs, RARs, and RORs
ABSTRACT Vitamin A (retinol) and its metabolites play many physiological roles including cell differentiation, cell proliferation, energy homeostasis, circadian rhythm and immune response. Vitamin A and its metabolites are known to act through retinoid acid receptors (RARs), retinoid-related orphan receptors (RORs) and retinoid x receptors (RXRs). These receptors are also important drug targets, although theRead More