A5048267141- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- Pharmacogenetics and Drug Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Safe Handling of Antineoplastic Drugs
- Estrogen and related hormone effects
- Chronic Lymphocytic Leukemia Research
- Contact Dermatitis and Allergies
- RNA Interference and Gene Delivery
- Occupational exposure and asthma
- Pharmaceutical studies and practices
- NF-κB Signaling Pathways
- Biotechnology and Related Fields
- Protein Tyrosine Phosphatases
- Thyroid Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Virus-based gene therapy research
- Computational Drug Discovery Methods
- Immunotoxicology and immune responses
- Silicon and Solar Cell Technologies
- Drug Transport and Resistance Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Steroid Chemistry and Biochemistry
- Nerve injury and regeneration
Biogen (United States)
2017-2025
Entegris (United States)
2022
Amgen (United States)
2016
Pfizer (United States)
2008-2013
Target (United States)
2013
National Institutes of Health
2008
National Institute of Environmental Health Sciences
2006
Pennsylvania State University
2003-2006
Triangle
2006
Like other nuclear receptors, the peroxisome proliferator-activated receptors (PPARs) use a wide variety of protein-protein interactions to properly regulate transcription target genes. In an attempt identify novel PPAR-interacting proteins, cDNA expression library was screened with bacterially expressed PPARalpha. One genes identified as PPARalpha-associated protein by interaction cloning CREB-binding protein/p300-interacting transactivator ED-rich tail 2 (CITED2, also called...
The nuclear receptors CAR and PXR were first characterized as xenosensing transcription factors regulating the induction of phase I II xenobiotic-metabolizing enzymes well transporters in response to exogenous stimuli. It has now become clear, however, that these cross-talk with endogenous stimuli well, which extends their regulation various physiological processes such energy metabolism cell growth. As recognition function widened, molecular mechanism evolved from simple protein–DNA binding...
The nuclear receptor (NR) peroxisome proliferator-activated receptor-α (PPARα) mediates the effects of several hypolipidemic drugs, endogenous fatty acids, and proliferators. Despite belonging to a class NR not known interact with cytosolic chaperone complexes, we have recently shown that PPARα interacts heat shock protein 90 (Hsp90), although biological consequence this association was unknown. In present study, directly associated Hsp90 in vitro much greater extent than either PPARβ or...
Multiple Sclerosis is a chronic autoimmune neurodegenerative disorder of the central nervous system (CNS) that characterized by inflammation, demyelination, and axonal injury leading to permeant disability. In early stage MS, inflammation primary driver disease progression. There remains an unmet need develop high efficacy therapies with superior safety profiles prevent processes Herein, we describe discovery BIIB091, structurally distinct orthosteric ATP competitive, reversible inhibitor...
Autoreactive B cell-derived antibodies form immune complexes that likely play a pathogenic role in autoimmune diseases. In systemic lupus erythematosus (SLE), these bind Fc receptors on myeloid cells and induce proinflammatory cytokine production by monocytes NETosis neutrophils. Bruton's tyrosine kinase (BTK) is non-receptor signals downstream of plays transduction antibody expression following cell activation. Given the roles BTK both sensing autoreactive antibodies, inhibitors activity...
We observed that the level of reverse triiodothyronine (rT3) was significantly increased after partial hepatectomy (PH) in both wild-type and constitutively active/androstane receptor (CAR) knockout (KO) mice, treatment with phenobarbital (PB), a CAR activator, PH decreased rT3 to restore its original only mice. On other hand, no significant changes total T3 or free serum were either KO mice PB. Type 1 deiodinase (D1) activity expression reduced by up-regulated PB CAR-dependent manner. In...
Recombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons in the dorsal root ganglia (DRG) and trigeminal (TG) has been observed non-human primates (NHPs) following intravenous (IV) intrathecal (IT) delivery. Administration recombinant AAV encoding a human protein transgene via single intra-cisterna magna (ICM) injection New Zealand white rabbits resulted histopathology changes very similar to NHPs: mononuclear cell infiltration, degeneration/necrosis neurons, nerve...
Genome-wide association (GWA) studies have described a large number of new candidate genes that contribute to Type 2 Diabetes (T2D). In some cases, small clusters are implicated, rather than single gene, and in all the genetic contribution is not defined through effects on specific organ, such as pancreas or liver. There significant need develop use human cell-based models examine these may glucose regulation. We describe development primary hepatocyte model adjusts disposition according...
The ligand-dependent recruitment of coactivators to peroxisome proliferator-activated receptor-alpha (PPARalpha) was examined. PPAR-binding protein (PBP), PPARgamma coactivator-1alpha (PGC-1alpha), steroid receptor coactivator-1 (SRC-1), and CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2) affected PPARalpha activity in the presence Wy-14,643. effects on light increased or decreased expression these were qualitatively different depending ligand Diminished PGC-1alpha, SRC-1,...
Glucokinase (GK) catalyzes the phosphorylation of glucose to glucose-6-phosphate. We present structure-activity relationships leading discovery AM-2394, a structurally distinct GKA. AM-2394 activates GK with an EC50 60 nM, increases affinity for by approximately 10-fold, exhibits moderate clearance and good oral bioavailability in multiple animal models, lowers excursion following tolerance test ob/ob mouse model diabetes.