A5070956637- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Sulfur Compounds in Biology
- Ocular Surface and Contact Lens
- Crystallization and Solubility Studies
- Intraocular Surgery and Lenses
- Advanced Drug Delivery Systems
- Lung Cancer Treatments and Mutations
- X-ray Diffraction in Crystallography
- Retinal and Macular Surgery
- Biomedical Research and Pathophysiology
- Amino Acid Enzymes and Metabolism
- Cancer therapeutics and mechanisms
- Healthcare and Venom Research
- Drug Transport and Resistance Mechanisms
- RNA modifications and cancer
- Retinal Imaging and Analysis
- Epigenetics and DNA Methylation
- Circadian rhythm and melatonin
- Adenosine and Purinergic Signaling
- Genetics, Bioinformatics, and Biomedical Research
- Acute Myeloid Leukemia Research
- Invertebrate Immune Response Mechanisms
- Advancements in Transdermal Drug Delivery
- Lung Cancer Research Studies
University of Southern California
2000-2024
ChemDiv (United States)
2023
Pfizer (United States)
2008-2021
Allergan (United States)
2018-2021
AbbVie (United States)
2021
Pharmaceutical Biotechnology (Czechia)
2002-2003
Southern California University for Professional Studies
2000-2003
Rogers (United States)
2000
A new series of lactam-derived EZH2 inhibitors was designed via ligand-based and physicochemical-property-based strategies to address metabolic stability thermodynamic solubility issues associated with previous lead compound 1. The incorporated an sp3 hybridized carbon atom at the 7-position lactam moiety present in 1 as a replacement for dimethylisoxazole group. This transformation enabled optimization physicochemical properties potency compared Analysis relationships between calculated log...
The study objective was to investigate molecular thermodynamic properties of approved ophthalmic drugs and derive a framework outlining physicochemical design space for product development. Unlike the methodology used obtain descriptors assessment drug-like by Lipinski's Rule 5 (Ro5), this work presents retrospective approach based on in silico analysis beyond Ro5 parameters (ie, free energy distribution/partitioning octanol/water, dynamic polar surface area, distribution coefficient,...
A new enhancer of zeste homolog 2 (EZH2) inhibitor series comprising a substituted phenyl ring joined to dimethylpyridone moiety via an amide linkage has been designed. preferential torsion that improved the binding properties compounds was identified for this computational analysis. Cyclization linker resulted in six-membered lactam analogue, compound 18. This transformation significantly ligand efficiency/potency cyclized relative its acyclic analogue. Additional optimization...
Age-related Macular Degeneration (AMD) is the leading cause of visual impairment and blindness in elderly developed countries. Neovascular/exudative (wet) AMD aggressive form can involve choroidal neovascularization vascular leakage. Anti-vascular endothelial growth factor (anti-VEGF) medications have significantly improved treatment wet-AMD. However, only approximately 40% patients obtain full benefit from anti-VEGF therapy are given by intravitreal injection. Axitinib, a small molecule...
The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway is a frequently dysregulated in human cancer, and PI3Kα one the most mutated kinases cancer. A PI3Kα-selective inhibitor may provide opportunity to spare patients side effects associated with broader inhibition class I PI3K family. Here, we describe our efforts discover by applying structure-based drug design (SBDD) computational analysis. novel series compounds, exemplified 2,2-difluoroethyl...
The antiglaucoma drugs dorzolamide (1) and brinzolamide (2) lower intraocular pressure (IOP) by inhibiting the carbonic anhydrase (CA) enzyme to reduce aqueous humor production. introduction of a nitric oxide (NO) donor into alkyl side chain has led discovery NO-dorzolamide 3a NO-brinzolamide 4a, which could IOP through two mechanisms: CA inhibition decrease secretion (reduce inflow) NO release increase drainage (increase outflow). Compounds 4a have shown improved efficacy lowering in both...
In the eye, nitric oxide (NO) is involved in regulation of intraocular pressure (IOP) and ocular blood flow. The main purpose this study was to measure kinetics NO release from donors cells tissues using vivo vitro models demonstrate link between with functional effect, IOP. Nitric measured human a fluorescent dye, diaminofluorescein (DAF), following treatment short-acting sodium nitroprusside (SNP) longer-acting S-nitroso-N-acetylpenicillamine (SNAP) donors. Both SNP SNAP were also...
Detecting and monitoring exocrine pancreatic damage during nonclinical clinical testing is challenging because classical biomarkers amylase lipase have limited sensitivity specificity. Novel for drug-induced injury are needed to improve safety assessment reduce late-stage attrition rates. In a series of studies, miR-216a miR-217 were evaluated as potential acute toxicity in rats. Our results revealed that almost exclusively expressed rat pancreas circulating significantly increased rats...
In our quest to develop a tissue-engineered tear secretory system, we have tried demonstrate active transepithelial ion fluxes across rabbit lacrimal acinar cell monolayers on polyester membrane scaffolds evaluate the bioelectrical properties of cultured cells. Purified gland cells were seeded onto inserts and confluency. Morphological evaluated by transmission electron microscopy immunofluorescence staining for Na + ,K -ATPase tight junction-associated protein occludin. Sections revealed...
A pyridone-derived phosphate prodrug of an enhancer zeste homolog 2 (EZH2) inhibitor was designed and synthesized to improve the inhibitor's aqueous solubility. This (compound 5) profiled in pharmacokinetic experiments assess its ability deliver corresponding parent compound 2) animals vivo following oral administration. Results from these studies showed that efficiently converted vivo. In separate experiments, demonstrated impressive tumor growth inhibition a diffuse large B-cell lymphoma...
Background: The interstitial testicular Leydig cells are responsible for the production of testosterone, which functionally deteriorate with normal aging. Decreased expression mitochondrial steroidogenic interactome proteins and diminished function in aging suggest that dynamics play a role maintaining adequate levels testosterone. Optic atrophy 1 (OPA1) protein regulates cristae formation many cell types. Previous studies showed increasing OPA1 dysfunctional restored recovered androgen to...
The use of l-carnosine as an excipient in topical ophthalmic formulations containing gellan gum, a carbohydrate polymer with in-situ gelling properties upon mixing mammalian tear fluid, was developed novel platform to extend precorneal duration. Specific utilisation buffer gum carrying vehicles characterised.Buffer capacity evaluated using 7.5, 13.3, and 44.2 mm pH range 5.5-7.5. Accelerated chemical stability determined by HPLC at concentrations 5-100 mm. Combinations 7.5 0.06-0.6% (w/v)...
Metabolism and transport of cysteine are critical for maintenance the intracellular glutathione (GSH) level. In this study, mechanisms L-cystine regulation GSH biosynthesis in absence or presence NO-induced oxidant stress were investigated primary cultured rabbit conjunctival epithelial cells (RCECs).RCECs grown membrane filters to exhibit tight barrier properties. Uptake transepithelial determined extracellular Na(+). was at 10 minutes after (14)C-L-cystine instillation into apical (a)...