A5073483421- Receptor Mechanisms and Signaling
- Orthopaedic implants and arthroplasty
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- 3D Printing in Biomedical Research
- Bone health and osteoporosis research
- Bone and Joint Diseases
- Biosensors and Analytical Detection
- Ergonomics and Musculoskeletal Disorders
- Cannabis and Cannabinoid Research
- Protein Interaction Studies and Fluorescence Analysis
- Bacteriophages and microbial interactions
- Bone health and treatments
- Renal Diseases and Glomerulopathies
- Protein Kinase Regulation and GTPase Signaling
- Multiple Myeloma Research and Treatments
- Bone Metabolism and Diseases
- Pancreatic function and diabetes
- Chemokine receptors and signaling
- Molecular Biology Techniques and Applications
- Engineering Technology and Methodologies
- Spatial Neglect and Hemispheric Dysfunction
- Medical and Biological Sciences
- RNA and protein synthesis mechanisms
- Digestive system and related health
Merck & Co., Inc., Rahway, NJ, USA (United States)
2015-2021
Bristol-Myers Squibb (United States)
2020-2021
Target (United States)
2021
Seton Hall University
2020
Kallyope (United States)
2020
Medical University of South Carolina
2008
The human intestinal mucosa is a critical site for absorption, distribution, metabolism, and excretion (ADME)/Tox studies in drug development difficult to recapitulate vitro. Using bioprinting, we generated three-dimensional (3D) tissue composed of primary epithelial cells myofibroblasts with architecture function model the native intestine. 3D demonstrates polarized epithelium tight junctions specialized cell types expresses functional inducible CYP450 enzymes. tissues develop physiological...
Drug-induced gastrointestinal toxicity (GIT) is a common treatment-emergent adverse event that can negatively impact dosing, thereby limiting efficacy and treatment options for patients. An in vitro assay of GIT needed to address patient variability, mimic the microphysiology gut, accurately predict drug-induced GIT. Primary human ileal organoids (termed 'enteroids') have proven useful stimulating intestinal stem cell proliferation differentiation multiple types present gut epithelium....
A new subseries of ROMK inhibitors exemplified by 28 has been developed from the initial screening hit 1. The excellent selectivity for inhibition over related ion channels and pharmacokinetic properties across preclinical species support further evaluation as a mechanism diuretic. Robust pharmacodynamic effects in both SD rats dogs have demonstrated.
ABSTRACT Human myeloma bone disease (MBD) occurs when malignant plasma cells migrate to the marrow and commence inimical interactions with stromal cells, disrupting skeletal remodeling process. The simultaneously suppress osteoblastic formation while promoting excessive osteoclastic resorption. This metabolism imbalance produces osteolytic lesions that cause chronic pain reduce trabecular cortical structural integrity, often culminate in pathological fractures. Few models exist enable...
Quantitative reverse transcription PCR (qRT-PCR) is a valuable tool for characterizing the effects of inhibitors on viral replication. The amplification target genes through use specifically designed fluorescent probes and primers provides reliable method quantifying RNA. Due to reagent costs, these assays compound evaluation limited. Until recently, inability accurately dispense low volumes qRT-PCR assay reagents precluded routine this in drug discovery. Acoustic dispensing has become an...
G-protein-coupled receptors (GPCRs) are modulated by many marketed drugs, and as such, they continue to be key targets for drug discovery development. Many GPCR at Merck Research Laboratories (MRL) profiled using homogenous time-resolved fluorescence (HTRF) inositol monophosphate (IP-1) cell-based functional assays adherent cells in 384-well microplates. Due discrepancies observed across several vitro supporting lead optimization structure–activity relationship (SAR) efforts, different assay...
We have developed and validated label-free, liquid chromatography-mass spectrometry (LC-MS)-based equilibrium direct competition binding assays to quantitate small-molecule antagonist recombinant human mouse BLT1 receptors expressed in HEK 293 cell membranes. Procedurally, these involve (1) equilibration of the receptor probe ligand, with or without a competitor; (2) vacuum filtration through cationic glass fiber filters separate receptor-bound from free ligand; (3) LC-MS analysis selected...
High-throughput phenotypic screening is a key driver for the identification of novel chemical matter in drug discovery challenging targets, especially those with an unclear mechanism pathology. For toxic or gain-of-function proteins, small-molecule suppressors are targeting/therapeutic strategy that has been successfully applied. As other high-throughput screens, and proper assays critical identifying selective target interest. We executed suppressor screen to identify compounds specifically...
Fibrosis or accumulation of extracellular matrix is an evolutionarily conserved mechanism adopted by organism as a response to chronic injury. Excessive fibrosis, however, leads disruption organ homeostasis and common feature many diseases. G protein-coupled receptors (GPCRs) are important cell signaling mediators represent molecular targets for Food Drug Administration-approved drugs. To identify new we used synthetic GPCR system named designed exclusively activated designer drugs (DREADDs)...