Publications

Naivety about promiscuous, assay-duping molecules is polluting the literature and wasting resources, warn Jonathan Baell and Michael A. Walters

Spheroid-based cellular screening approaches represent a highly physiologic experimental setup to identify novel anticancer drugs and an innovative preclinical model to reduce the high failure rate of anticancer compounds in clinical trials. The resazurin reduction (RR) assay, known as the alamarBlue or CellTiter-Blue assay, is frequently used to determine cell viability/proliferation capacity in eukaryotic cells. […]

Neuroblastoma (NB) is a pediatric tumor of the sympathetic nervous system, which is often associated with elevated catecholamines. More than half of patients with metastatic NB relapse and survival is extremely poor with current therapies. In a high-throughput screen of FDA-approved drugs we identified anti-NB activity for the nonselective β-adrenergic receptor antagonist propranolol hydrochloride. Propranolol […]

This review highlights the concepts, recent applications and limitations of High Throughput Screening (HTS) flow cytometry-based efflux inhibitory assays. This platform has been employed in mammalian and yeast efflux systems leading to the identification of small molecules with transporter inhibitory capabilities. This technology offers the possibility of substrate multiplexing and may promote novel strategies targeting […]

PERK is serine/threonine kinase localized to the endoplasmic reticulum (ER) membrane. PERK is activated and contributes to cell survival in response to a variety of physiological stresses that affect protein quality control in the ER, such as hypoxia, glucose depravation, increased lipid biosynthesis, and increased protein translation. Pro-survival functions of PERK are triggered by such […]

Motor neuron disorders (MNDs) are a clinically heterogeneous group of neurological diseases characterized by progressive degeneration of motor neurons, and share some common pathological pathways. Despite remarkable advances in our understanding of these diseases, no curative treatment for MNDs exists. To better understand the pathogenesis of MNDs and to help develop new treatments, the establishment […]

Antibiotic resistance is a growing health concern, and new avenues of antimicrobial drug design are being actively sought. One suggested pathway to be targeted for inhibitor design is that of iron scavenging through siderophores. Here we present a high throughput screen to the isochorismate-pyruvate lyase of Pseudomonas aeruginosa, an enzyme required for the production of […]

Duchenne muscular dystrophy (DMD) is caused by a lack of the dystrophin protein and has no effective treatment at present. Zebrafish provide a powerful in vivo tool for high-throughput therapeutic drug screening for the improvement of muscle phenotypes caused by dystrophin deficiency. Using the dystrophin-deficient zebrafish, sapje, we have screened a total of 2640 compounds […]

Alternative splicing of pre-mRNAs is an important mechanism that regulates cellular function in higher eukaryotes. A growing number of human genetic diseases involve splicing defects that are directly connected to their pathology. In myotonic dystrophy type 1 (DM1), several clinical manifestations have been proposed to be the consequence of tissue-specific missplicing of numerous genes. These […]