success-story

High Throughput Screening (HTS) is a standard technique widely used to find hit compounds in drug discovery projects. The high costs associated with such experiments have highlighted the need to carefully design screening libraries in order to avoid wasting resources. Molecular diversity is an established concept that has been used to this end for many […]

We previously reported the use of the cheap and fast-growing nematode Caenorhabditis elegans to search for molecules, which reduce muscle degeneration in a model for Duchenne Muscular Dystrophy (DMD). We showed that Prednisone, a steroid that is generally prescribed as a palliative treatment to DMD patients, also reduced muscle degeneration in the C. elegans DMD […]

Resistance to the commonly used azole antifungal fluconazole (FLC) can develop due to overexpression of ATP-binding cassette (ABC) and major facilitator superfamily (MFS) plasma membrane transporters. An approach to overcoming this resistance is to identify inhibitors of these efflux pumps. We have developed a pump assay suitable for high-throughput screening (HTS) that uses recombinant Saccharomyces […]

Glycolytic isozymes that are restricted to the male germline are potential targets for the development of reversible, non-hormonal male contraceptives. GAPDHS, the sperm-specific isoform of glyceraldehyde-3-phosphate dehydrogenase, is an essential enzyme for glycolysis making it an attractive target for rational drug design. Toward this goal, we have optimized and validated a high-throughput spectrophotometric assay for […]

BACKGROUND: Genetic long QT (LQT) syndrome is a life-threatening disorder caused by mutations that result in prolongation of cardiac repolarization. Recent work has demonstrated that a zebrafish model of LQT syndrome faithfully recapitulates several features of human disease, including prolongation of ventricular action potential duration, spontaneous early afterdepolarizations, and 2:1 atrioventricular block in early stages […]

The Prestwick and NIH chemical libraries were screened for drugs that protect baker’s yeast from sugar-induced cell death (SICD). SICD is triggered when stationary-phase yeast cells are transferred from spent rich medium into water with 2% glucose and no other nutrients. The rapid, apoptotic cell death occurs because reactive oxygen species (ROS) accumulate. We found […]

Two known zebrafish dystrophin mutants, sapje and sapje-like (sap(c/100)), represent excellent small-animal models of human muscular dystrophy. Using these dystrophin-null zebrafish, we have screened the Prestwick chemical library for small molecules that modulate the muscle phenotype in these fish. With a quick and easy birefringence assay, we have identified seven small molecules that influence muscle […]

The casitas B-lineage lymphoma (Cbl) proteins play an important role in regulating signal transduction pathways by functioning as E3 ubiquitin ligases. The Cbl proteins contain a conserved tyrosine kinase binding (TKB) domain that binds more than a dozen proteins, including protein tyrosine kinases (PTKs), in a phosphorylation-dependent manner. The cell surface expression levels of the […]

High-throughput screening (HTS) is a well-established technology which can test up to several million compounds in a few weeks. Despite these appealing capabilities, available resources and high costs may limit the number of molecules screened, making diversity analysis a method of choice to design and prioritize screening libraries. With a constantly increasing number of molecules […]

GPR35 is a poorly characterized G protein-coupled receptor (GPCR) that has been suggested as a potential therapeutic target for the treatment of diabetes, hypertension and asthma. Two endogenously produced ligands have been suggested as activators of GPR35, although the relevance of these remains unclear. Recently, a series of surrogate agonist ligands and the first antagonists […]