A5050507826- Estrogen and related hormone effects
- Prostate Cancer Treatment and Research
- Retinoids in leukemia and cellular processes
- Peroxisome Proliferator-Activated Receptors
- Cancer, Lipids, and Metabolism
- Cholesterol and Lipid Metabolism
- Lung Cancer Research Studies
- Neuroendocrine Tumor Research Advances
- Advanced Breast Cancer Therapies
- Antioxidant Activity and Oxidative Stress
- Drug Transport and Resistance Mechanisms
- Radiopharmaceutical Chemistry and Applications
- HER2/EGFR in Cancer Research
- Gyrotron and Vacuum Electronics Research
- Peptidase Inhibition and Analysis
- Cancer therapeutics and mechanisms
- Cardiac pacing and defibrillation studies
- Hormonal and reproductive studies
- Computational Drug Discovery Methods
- Photodynamic Therapy Research Studies
- Click Chemistry and Applications
- Axon Guidance and Neuronal Signaling
- Synthesis and biological activity
- Cardiac Arrest and Resuscitation
- Cardiac electrophysiology and arrhythmias
Edison Pharmaceuticals (United States)
2016
Tracon Pharmaceuticals (United States)
2015
Memorial Sloan Kettering Cancer Center
2011-2012
University of California, Los Angeles
2011
University of California, San Diego
2010
Exelixis (United States)
2009
The Seattle Institute for Cardiac Research
2008
Xalud Therapeutics (United States)
2002-2004
Howard Hughes Medical Institute
2002
The University of Texas Southwestern Medical Center
2002
Abstract Continued reliance on the androgen receptor (AR) is now understood as a core mechanism in castration-resistant prostate cancer (CRPC), most advanced form of this disease. While established and novel AR pathway–targeting agents display clinical efficacy metastatic CRPC, dose-limiting side effects remain problematic for all current agents. In study, we report discovery development ARN-509, competitive inhibitor that fully antagonistic to overexpression, common important feature CRPC....
Recent studies have identified the liver X receptors (LXRα and LXRβ) as important regulators of cholesterol metabolism transport. LXRs control transcription genes critical to a range biological functions including regulation high density lipoprotein metabolism, hepatic catabolism, intestinal sterol absorption. Although LXR activity has been proposed be for physiologic lipid transport, direct evidence linking signaling pathways pathogenesis cardiovascular disease yet established. In this...
The most common location of out-of-hospital sudden cardiac arrest is the home, a situation in which emergency medical services are challenged to provide timely care. Consequently, home use an automated external defibrillator (AED) might offer opportunity improve survival for patients at risk.
Complications of atherosclerotic cardiovascular disease due to elevated blood cholesterol levels are the major cause death in Western world. The liver X receptors, LXRalpha and LXRbeta (LXRs), ligand-dependent transcription factors that act as sensors coordinately control genes involved lipid homeostasis well macrophage inflammatory gene expression. LXRs regulate balance through activation ATP-binding cassette transporters promote transport excretion from liver, intestine, macrophage....
Liver X receptors (LXRs) regulate the expression of genes involved in cholesterol and fatty acid homeostasis, including for ATP-binding cassette transporter A1 (ABCA1) sterol response element binding protein 1 (SREBP1). Loss LXR leads to derepression ABCA1 gene macrophages intestine, while SREBP1c remains transcriptionally silent. Here we report that high-density-lipoprotein (HDL) levels are increased LXR-deficient mice, suggesting possibly other target selected tissues is sufficient result...
The farnesoid X receptor (FXR; NR1H4) regulates bile acid and lipid homeostasis by acting as an intracellular acid-sensing transcription factor. Several identified FXR target genes serve critical roles in the synthesis transport of acids well metabolism. Here we used Affymetrix micro-array Northern analysis to demonstrate that two enzymes involved conjugation taurine glycine, namely acid-CoA synthetase (BACS) acid-CoA: amino <i>N</i>-acetyltransferase (BAT) are induced rat liver. Analysis...
Azepino[4,5-b]indoles have been identified as potent agonists of the farnesoid X receptor (FXR). In vitro and in vivo optimization has led to discovery 6m (XL335, WAY-362450) a potent, selective, orally bioavailable FXR agonist (EC(50) = 4 nM, Eff 149%). Oral administration LDLR(-/-) mice results lowering cholesterol triglycerides. Chronic an atherosclerosis model significant reduction aortic arch lesions.
ER-targeted therapeutics provide valuable treatment options for patients with ER+ breast cancer, however, current relapse and mortality rates emphasize the need improved therapeutic strategies. The recent discovery of prevalent ESR1 mutations in relapsed tumors underscores a sustained reliance advanced on ERα signaling, provides strong rationale continued targeting ERα. Here we describe GDC-0810, novel, non-steroidal, orally bioavailable selective ER downregulator (SERD), which was...
Recent studies have identified the liver X receptors (LXRα and LXRβ) as important regulators of cholesterol lipid metabolism. Although originally liver-enriched transcription factors, LXRs are also expressed in skeletal muscle, a tissue that accounts for ∼40% human total body weight is major site glucose utilization fatty acid oxidation. Nevertheless, no yet addressed functional role muscle. In this work we utilize combination vivoand vitro analysis to demonstrate can functionally regulate...
Overexpression of somatostatin receptors (SSTR), particularly SSTR2, is found in gastroenteropancreatic neuroendocrine tumors (GEP-NET), and subsets other solid such as small-cell lung cancer (SCLC). SCLC accounts for approximately 13% to 15% lacks effective therapeutic options. IHC analysis indicates that up 50% are SSTR2-positive, with a substantial subset showing high homogenous expression. Peptide receptor radionuclide therapy radiolabeled analogue, Lu-177 DOTATATE, has been approved...
We have previously shown that a retinoid X receptor (RXR)-selective ligand (a rexinoid), called LGD1069, is highly efficacious in both the chemoprevention and chemotherapy for N-nitrosomethylurea-induced rat mammary carcinomas. To evaluate possible role rexinoids breast cancer therapy further, we designed characterized novel carcinogen-induced model to mimic clinical situation which tumors of patients stop responding tamoxifen develop resistance this drug.Rats with experimentally induced...
The liver X receptors LXRα and LXRβ play critical roles in maintaining lipid homeostasis by functioning as transcription factors that regulate genetic networks controlling the transport, catabolism, excretion of cholesterol. studies described this report examine individual anti-atherogenic activity determine ability each subtype to mediate biological response LXR agonists. Utilizing knockouts Ldlr−/− background, we demonstrate has a dominant role limiting atherosclerosis vivo. Functional...
The conventional treatment of uterine leiomyomas, or fibroids, with gonadotropin-releasing hormone (GnRH) agonists is often associated serious side effects, necessitating short-term, palliative use this therapy. Therefore, we examined a retinoid X receptor (RXR)-selective ligand, LGD1069, as possible for leiomyoma. LGD1069 has demonstrated efficacy chemopreventive agent in the N-nitroso-N-methylurea (NMU)-induced rat mammary carcinoma model and therapeutic several epithelial tumor models....