A5003496917- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Hormonal and reproductive studies
- Ion channel regulation and function
- Hormonal Regulation and Hypertension
- Pharmacological Receptor Mechanisms and Effects
- Steroid Chemistry and Biochemistry
- Ion Channels and Receptors
- Ion Transport and Channel Regulation
- Nicotinic Acetylcholine Receptors Study
- Synthesis and Biological Evaluation
- Signaling Pathways in Disease
- Adenosine and Purinergic Signaling
- Piperaceae Chemical and Biological Studies
- Phenothiazines and Benzothiazines Synthesis and Activities
- Helicobacter pylori-related gastroenterology studies
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Herbal Medicine Research Studies
- Endometriosis Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Carbohydrate Chemistry and Synthesis
- Phytochemicals and Antioxidant Activities
- Peptidase Inhibition and Analysis
- Cholinesterase and Neurodegenerative Diseases
GlaxoSmithKline (United States)
2008-2024
South College
2019-2024
GlaxoSmithKline (Netherlands)
2023
Pathways Behavioral Services
2019
GlaxoSmithKline (United Kingdom)
2009
University of Virginia
2004-2005
Abstract Androgens, through their actions on the androgen receptor (AR), are required for development of prostate and contribute to pathologic growth dysregulation observed in cancers. Consequently, ablation has become an essential component pharmacotherapy cancer. In this study, we explored utility targeting processes downstream AR as alternate approach therapy. Specifically, show that serum glucocorticoid-regulated kinase 1 (SGK1) gene is androgen-regulated target cellular models...
GSK2798745, a clinical candidate, was identified as an inhibitor of the transient receptor potential vanilloid 4 (TRPV4) ion channel for treatment pulmonary edema associated with congestive heart failure. We discuss lead optimization this novel spirocarbamate series and specifically focus on our strategies solutions achieving desirable potency, rat pharmacokinetics, physicochemical properties. highlight use conformational bias to deliver potency volume distribution unbound clearance enable...
GSK3527497, a preclinical candidate for the inhibition of TRPV4, was identified starting from previously reported pyrrolidine sulfonamide TRPV4 inhibitors 1 and 2. Optimization projected human dose accomplished by specifically focusing on in vivo pharmacokinetic parameters CLu, Vdssu, MRT. We highlight use conformational changes as novel approach to modulate Vdssu present results that suggest molecular-shape-dependent binding tissue components governs addition bulk physicochemical...
Investigation of TRPV4 as a potential target for the treatment pulmonary edema associated with heart failure generated novel series acyclic amine inhibitors displaying exceptional potency and PK properties. The arose through scaffold hopping approach, which relied on use an internal H-bond to replace saturated heterocyclic ring. Optimization lead investigation both aryl regions revealed approaches increase substituents believed enhance separate intramolecular intermolecular interactions. A...
A series of diarylurea inhibitors the cardiac-specific kinase TNNI3K were developed to elucidate biological function and evaluate as a therapeutic target for treatment cardiovascular diseases. Utilizing structure-based design, enhancements in selectivity engineered into series, capitalizing on established X-ray crystal structures TNNI3K, VEGFR2, p38α, B-Raf. Our efforts culminated discovery an vivo tool compound 47 (GSK329), which exhibited desirable potency rat pharmacokinetic properties...
<div>Abstract<p>Androgens, through their actions on the androgen receptor (AR), are required for development of prostate and contribute to pathologic growth dysregulation observed in cancers. Consequently, ablation has become an essential component pharmacotherapy cancer. In this study, we explored utility targeting processes downstream AR as alternate approach therapy. Specifically, show that serum glucocorticoid-regulated kinase 1 (<i>SGK1</i>) gene is...
Supplementary Data from Development of a Small-Molecule Serum- and Glucocorticoid-Regulated Kinase-1 Antagonist Its Evaluation as Prostate Cancer Therapeutic
Supplementary Data from Development of a Small-Molecule Serum- and Glucocorticoid-Regulated Kinase-1 Antagonist Its Evaluation as Prostate Cancer Therapeutic
<div>Abstract<p>Androgens, through their actions on the androgen receptor (AR), are required for development of prostate and contribute to pathologic growth dysregulation observed in cancers. Consequently, ablation has become an essential component pharmacotherapy cancer. In this study, we explored utility targeting processes downstream AR as alternate approach therapy. Specifically, show that serum glucocorticoid-regulated kinase 1 (<i>SGK1</i>) gene is...
The virally encoded 3-chymotrypsin-like protease (3CLpro) is a well-validated drug target for the inhibition of coronaviruses including Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Most inhibitors 3CLpro are peptidomimetic, with g-lactam in place Gln at P1 position pseudopeptide chain. An effort was pursued to identify viable alternative mimetic which would improve physicochemical properties while retaining affinity target. Discovery 2-tetrahydrofuran as suitable replacement...