A5024224859- Rheumatoid Arthritis Research and Therapies
- Autoimmune and Inflammatory Disorders Research
- Peroxisome Proliferator-Activated Receptors
- melanin and skin pigmentation
- Cytokine Signaling Pathways and Interactions
- Systemic Lupus Erythematosus Research
- Adipose Tissue and Metabolism
- Chronic Lymphocytic Leukemia Research
- Biosimilars and Bioanalytical Methods
- Metabolism, Diabetes, and Cancer
- Herpesvirus Infections and Treatments
- Biotin and Related Studies
- Atherosclerosis and Cardiovascular Diseases
- Biochemical Analysis and Sensing Techniques
- Pharmacological Effects of Natural Compounds
- Peripheral Neuropathies and Disorders
- Cancer, Lipids, and Metabolism
- Lymphoma Diagnosis and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Olfactory and Sensory Function Studies
- Hormonal Regulation and Hypertension
- Skin Protection and Aging
- Cholesterol and Lipid Metabolism
- Computational Drug Discovery Methods
- Colorectal and Anal Carcinomas
AbbVie (United States)
2015-2025
AbbVie (Japan)
2025
Heinz Optical Engineering (United States)
2016
Icahn School of Medicine at Mount Sinai
2014
The University of Adelaide
2014
Royal Adelaide Hospital
2014
Methodist Hospital
2014
University of Illinois Chicago
2014
University of Chicago
2013-2014
Houston Methodist
2014
Adipocyte differentiation is regulated both positively and negatively by external growth factors such as insulin, platelet-derived factor (PDGF), epidermal (EGF). A key component of the adipocyte process PPARγ, peroxisomal proliferator-activated receptor γ. To determine relationship between PPARγ activation stimulation in adipogenesis, we investigated effects PDGF EGF on PPARγ1 activity. treatment decreased ligand-activated transcriptional activity a transient reporter assay.In vivo...
Anti-cytokine therapies such as adalimumab, tocilizumab, and the small molecule JAK inhibitor tofacitinib have proven that cytokines their subsequent downstream signaling processes are important in pathogenesis of rheumatoid arthritis. Tofacitinib, a pan-JAK inhibitor, is first approved for treatment RA has been shown to be effective managing disease. However, phase 2 dose-ranging studies was associated with dose-limiting tolerability safety issues anemia. Upadacitinib (ABT-494) selective...
Objective To evaluate the efficacy and safety of ABT‐494, a selective JAK‐1 inhibitor, in patients with moderate‐to‐severe rheumatoid arthritis (RA) an inadequate response to methotrexate (MTX). Methods Three hundred RA receiving stable doses MTX were randomly assigned equally receive immediate‐release ABT‐494 at 3, 6, 12, or 18 mg twice daily, 24 once placebo for 12 weeks. The primary end point was proportion meeting American College Rheumatology 20% improvement criteria (achieving ACR20...
To determine functional differences between the two splice variants of PPARgamma (gamma1 and gamma2), we sought to selectively repress gamma2 expression by targeting engineered zinc finger repressor proteins (ZFPs) gamma2-specific promoter, P2. In 3T3-L1 cells, ZFP55 resulted in >50% reduction but had no effect on gamma1, whereas adipogenesis was similarly reduced 50%. However, ZFP54 virtually abolished both gamma1 expression, completely blocked adipogenesis. Overexpression exogenous...
The antidiabetic thiazolidinediones, which include troglitazone and rosiglitazone, are ligands for the nuclear receptor peroxisome proliferator-activated (PPAR)-gamma exert their antihyperglycemic effects by regulation of PPAR-gamma-responsive genes. We report here that PPAR-gamma activation depends on experimental setting. Troglitazone acts as a partial agonist in transfected muscle (C2C12) kidney (HEK 293T) cells, producing submaximal transcriptional response (1.8- to 2.5-fold activation)...
The peroxisome proliferator-activated receptor-γ (PPARγ) transcription factor plays a pivotal role in adipocyte differentiation and metabolic regulation. transcriptional activity of PPARγ is positively modulated by ligand binding negatively regulated phosphorylation mediated the MEK/ERK signaling pathway. mouse PPARγ1 at Ser82 ERK causes decrease both basal ligand-dependent activity. In this report we examined ability other mitogen-activated protein kinase family members to phosphorylate...
AMP-activated protein kinase (AMP-kinase) modulates many metabolic processes in response to fluctuations cellular energy status. Although most of its known targets are enzymes, it has been proposed that AMP-kinase might also regulate gene expression. Here we demonstrate the transcriptional coactivator p300 is a substrate AMP-kinase. Phosphorylation at serine 89 by dramatically reduced interaction, <i>in vitro</i> and vivo,</i> with nuclear receptors peroxisome proliferator-activated receptor...
c-Cbl-associated protein (CAP) is a signaling that interacts with both c-Cbl and the insulin receptor may be involved in specific insulin-stimulated tyrosine phosphorylation of c-Cbl. The restricted expression CAP cells metabolically sensitive to suggests an important potential role action. mRNA proteins are increased 3T3-L1 adipocytes by sensitizing thiazolidinedione drugs, which activators peroxisome proliferator-activated gamma (PPARgamma). stimulation PPARgamma results from...
Objective To compare the efficacy and safety of ABT‐494, a novel selective JAK‐1 inhibitor, with placebo in patients moderate‐to‐severe rheumatoid arthritis (RA) an inadequate response or intolerance to at least 1 anti–tumor necrosis factor (anti‐TNF) agent. Methods In this 12‐week, double‐blind, placebo‐controlled, dose‐ranging study, 276 RA receiving stable dose methotrexate (MTX) who had previously received treatment anti‐TNF agent were randomized equally receive immediate‐release ABT‐494...
Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental
Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in biosynthesis of monounsaturated fatty acids from saturated, long-chain acids. Studies with SCD1 knockout mice have established that these animals are lean and protected leptin deficiency-induced diet-induced obesity, greater whole body insulin sensitivity than wild-type animals. In this work, we discovered a series potent, selective, orally bioavailable inhibitors based on known pyridazine carboxamide template. The...
The nuclear receptor peroxisome proliferator-activated (PPAR)gamma plays a key role in regulating whole body glucose homeostasis and insulin sensitivity. Although it is expressed most highly adipose, also present at lower levels many tissues, including skeletal muscle. muscle PPARgamma metabolic regulation mediating the antidiabetic effects of thiazolidinediones not understood. goal this work was to examine molecular physiological activation cells. We found that pharmacological primary...
Background Upadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA). JAK inhibitors have been associated with increased risk herpes zoster (HZ) in patients RA. Objectives To evaluate incidence and factors HZ UPA-treated RA from UPA phase III clinical trial programme. Methods Exposure-adjusted incidence/event rates were determined receiving (monotherapy or combination therapy) six randomised trials (data cut-off on 30 June 2020). event...
Vitiligo is often associated with comorbid conditions that may increase economic burden and affect patients' health-related quality of life. No large-scale study has been published to date using claims databases evaluate the comorbidities among patients vitiligo. Herein, we comorbidity diagnosed vitiligo from US. This retrospective cohort analysis used Merative MarketScan Commercial Database. Eligible were between January 2008 December 2020 matched 1:4 (vitiligo:control) control subjects no...
To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol, The Evaluation of Choline Fenofibrate (ABT-335) on Carotid Intima-Media Thickness (cIMT) in Subjects Type IIb Dyslipidemia Residual Risk Addition Atorvastatin Therapy (FIRST) trial evaluated the effects fenofibric acid (FA) treatment cIMT patients mixed dyslipidemia atorvastatin.This multicenter, double-blind,...
The antidiabetic thiazolidinediones, which include troglitazone and rosiglitazone, are ligands for the nuclear receptor peroxisome proliferator-activated gamma (PPARgamma). Their antihyperglycemic effects seem to be linked regulation of PPARgamma-responsive genes. Here, we report characterization a specific PPARgamma antagonist that blocks several biological activities agonist rosiglitazone. PD068235 inhibited rosiglitazone-dependent transcriptional activity with an IC(50) 0.8 microM...
Starting from a rapidly metabolized adamantane 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor 22a, series of E-5-hydroxy-2-adamantamine inhibitors, exemplified by 22d and (+/-)-22f, was discovered. Many these compounds are potent inhibitors 11beta-HSD1 selective over 11beta-HSD2 for multiple species (human, mouse, rat), unlike other reported species-selective series. These have good cellular potency improved microsomal stability. Pharmacokinetic profiling in rodents...