A5047444345- Glaucoma and retinal disorders
- Inflammatory mediators and NSAID effects
- Cannabis and Cannabinoid Research
- Estrogen and related hormone effects
- Ocular Surface and Contact Lens
- Receptor Mechanisms and Signaling
- Eicosanoids and Hypertension Pharmacology
- Skin Protection and Aging
- Hair Growth and Disorders
- Retinal Diseases and Treatments
- melanin and skin pigmentation
- Proteoglycans and glycosaminoglycans research
- Pharmacological Receptor Mechanisms and Effects
- Spectroscopy Techniques in Biomedical and Chemical Research
- Delphi Technique in Research
- Spectroscopy and Chemometric Analyses
- Retinal Development and Disorders
- thermodynamics and calorimetric analyses
- Angiogenesis and VEGF in Cancer
- Plant Toxicity and Pharmacological Properties
- Ocular Diseases and Behçet’s Syndrome
- Flavonoids in Medical Research
- Otolaryngology and Infectious Diseases
- Pesticide Residue Analysis and Safety
- Forensic Toxicology and Drug Analysis
University of California, Irvine
2017-2023
Allergan (United States)
2010-2020
Allergan (Switzerland)
2012
β-catenin is a component of stable cell adherent complexes whereas its free form functions as transcription factor that regulate genes involved in oncogenesis and metastasis. Free eliminated by two adenomatous polyposis coli (APC)-dependent proteasomal degradation pathways regulated glycogen synthase kinase 3β (GSK3β) or p53-inducible Siah-1. Dysregulation turnover consequent to mutations critical the APC-dependent implicated cancers such colorectal cancer. We have identified novel retinoid...
Despite structural similarity with prostaglandin F(2 alpha), the ocular hypotensive agent bimatoprost (Lumigan; Allergan, Inc., Irvine, CA) shows unique pharmacology in vitro and functional activity vivo. Unfortunately, precise mechanisms that underlie bimatoprost's distinctive impact on aqueous humor dynamics are unclear. The purpose of present study was to investigate effects a novel prostamide-selective antagonist AGN 211334 human conventional drainage.Two model systems were used test...
Balding causes widespread psychological distress but is poorly controlled. The commonest treatment, minoxidil, was originally an antihypertensive drug that promoted unwanted hair. We hypothesized another serendipitous discovery, increased eyelash growth side-effects of prostamide F2α-related eyedrops for glaucoma, may be relevant scalp alopecias. Eyelash hairs and follicles are highly specialized remain unaffected by androgens inhibit stimulate many others. Therefore, we investigated whether...
Purpose.: The goal of this study was to functionally compare prostaglandin E2 (PGE2)-sensitive receptors in human primary cells involved conventional outflow. Methods.: expression profile (PG) cultures trabecular meshwork (TM) and Schlemm's canal (SC) were determined by quantitative-PCR. functional activities endogenous PGE2-sensitive evaluated using subtype-selective agonists antagonists with cell impedance technology. Results.: Agonist-sensitive EP1, EP2, EP4 present TM cells, all...
Bimatoprost is a widely used ocular hypotensive agent to treat glaucoma.It lowers intraocular pressure in humans by increasing both pressure-independent (uveoscleral) and pressure-dependent (conventional) aqueous humor outflow.The present study specifically examines bimatoprost effects on the cells that populate human outflow tissues.METHODS.The authors tested for prostamide receptor activation primary cultures of trabecular meshwork (TM), Schlemm's canal (SC), ciliary smooth muscle (CSM)...
Background and Purpose Prostamides are lipid mediators formed by COX ‐2‐catalysed oxidation of the endocannabinoid anandamide eliciting effects often opposed to those caused anandamide. may be when hydrolysis fatty acid amide hydrolase ( FAAH ) is physiologically, pathologically or pharmacologically decreased. Thus, therapeutic benefits inhibitors might attenuated concomitant production prostamide F 2 α . This loss benefit minimized compounds designed selectively antagonize receptors also...
Ligand activation of retinoic acid receptors (RARs) involves coordinated changes in their interaction with coregulatory molecules. Binding the agonist all-<i>trans</i>-retinoic to RAR results increased coactivator molecules as well a decreased corepressor Thus, an all-<i>trans-</i>retinoic antagonist might function either by preventing induction such events or, additionally, actively increasing repression via recruitment. We demonstrate that transcriptional activity constitutively active...
Purpose: To investigate the therapeutic potential of a prostacyclin (IP) receptor agonist for ocular inflammation and effect on immune cells. Methods: The anti-inflammatory activities cicaprost were determined in primary human monocyte-derived macrophages dendritic cells (MoDC), as well lipopolysaccharides (LPS)-induced rat uveitis model. Multiple cytokine release was measured by utilizing Luminex Technology. Prostacyclin Receptor expression detected reverse transcription–polymerase chain...
A polypharmacologic approach to prostanoid based anti-inflammatory therapeutics was undertaken in order exploit both the anti- and proinflammatory properties attributed various receptors. Multitargeting of selected receptors yielded a prototype compound, compound 1 (AGN 211377), that antagonizes prostaglandin D2 (DPs) DP1 (49) DP2 (558), E2 (EPs) EP1 (266) EP4 (117), receptor (FP) (61), thromboxane A2 (TP) (11) while sparing EP2, EP3, I2 (IPs); Kb values (in nanomoles) are given parentheses....
Purpose: Two features define the future of glaucoma therapeutics: (1) greatly improved ocular hypotensive efficacy and (2) a delivery method that improves patient convenience compliance. A highly efficacious extraordinarily long-acting agent PGN 9856-isopropyl ester represents potential next-generation anti-glaucoma drug. new periorbital drug route was also investigated. Methods: pharmacology determined by employing human cells, including prostanoid receptor transfectants, FLIPr or cellular...
Objectives As research in otolaryngology continues to expand rapidly, it is important identify core journals keep clinicians updated with the latest advances. This study first characterize otolaryngology. Methods Using h‐index and impact factor (IF), top 15 NLM‐indexed were selected for analysis. The references from all articles published these one randomized quarter compiled into a citation rank list, most cited journal ranked highest. Citation zonal distribution analysis was conducted of...
The purpose of these studies was to test the hypothesis that a selected polypharmacological approach for treating prostanoid-mediated component inflammatory diseases would produce therapeutic effect superior global inhibition prostaglandin (PG) biosynthesis by aspirin-like drugs. compound studied AGN 211377, which had been previously shown on cytokine release from human macrophages compared with cyclooxygenase (COX) inhibitors. 211377 antagonizes prostanoid D2 (DP)1, DP2, E2 (EP)1, EP4, F2α,...
The discovery of extended catalytic versatilities is great importance in both the chemistry and biotechnology fields. Fatty acid amide hydrolase (FAAH) belongs to amidase signature superfamily a major endocannabinoid inactivating enzyme using an atypical mechanism involving hydrolysis occasionally ester bonds. FAAH inhibitors are efficacious experimental models neuropathic pain, inflammation, anxiety, among others. We report new multitarget drug, AGN220653, containing carboxyamide-4-oxazole...
Background A single application of JV-GL1 substantially lowers non-human primate intraocular pressure (IOP) for about a week, independent dose. This highly protracted effect does not correlate with its ocular biodisposition or the once-daily dosing regimen other prostanoid EP 2 receptor agonists such as trapenepag omidenepag. The underlying pharmacological mechanism multiday extended activity is intriguing. present studies were intended to determine involvement in mediating long-term...
The purpose of these studies was (1) to investigate the ability human M1 phenotype macrophages secrete vascular endothelial growth factor (VEGF) and influence prostacyclin receptor (IP) stimulation (2) evaluate contribution proangiogenic prostanoid experimental choroidal neovascularization Methods: Human derived from primary blood mononuclear cells were functionally biased toward by using tumor necrosis α (TNFα). Experimental produced laser photocoagulation. Antagonist drugs RO-3244794 (IP...
Purpose: JV-GL1 is an efficacious, potent, and long-acting antiglaucoma agent, according to studies in ocular normotensive hypertensive monkeys. As obligatory step the drug development process, with exaggerated doses accelerated dosing schedule for were performed a second species (dog). Methods: Intraocular pressure (IOP) was measured by pneumatonometry conscious Beagle dogs, which remained throughout study gently restrained hand. Pupil diameter Optistick. Ocular surface hyperemia visually...
It has previously been reported that a prototypical compound (AGN 211377), which blocks pro-inflammatory prostanoid receptors (DP1, DP2, EP1, EP4, FP, TP) and leaves open IP EP2 so their anti-inflammatory properties could be exerted, produced superior inhibitory effects on cytokine release from human macrophages compared to cyclooxygenase (COX) inhibitors. This favorable activity profile translated into animal studies, with AGN 211377 exceeding the level of inhibition afforded by COX...