Despite advancements in therapies developed for the treatment of cancer, patient prognosis and mortality rates have improved minimally, and metastasis remains the primary cause of cancer mortality worldwide. An underlying mechanism promoting metastasis in many types of cancer is epithelial-mesenchymal transition (EMT). Here the authors report a novel 3D model of EMT and metastatic breast cancer...

Cofactor-independent phosphoglycerate mutase (iPGAM) is essential for the growth of C. elegans but is absent from humans, suggesting its potential as a drug target in parasitic nematodes such as Brugia malayi, a cause of lymphatic filariasis (LF). iPGAM's active site is small and hydrophilic, implying that it may not be druggable, but another binding site might permit allosteric inhibition. As ...

MOTIVATION Most data analysis tools for high-throughput screening (HTS) seek to uncover interesting hits for further analysis. They typically assume a low hit rate per plate. Hit rates can be dramatically higher in secondary screening, RNAi screening and in drug sensitivity testing using biologically active drugs. In particular, drug sensitivity testing on primary cells is often based on dose-r...

Deregulation of c-Myc plays a central role in the tumorigenesis of many human cancers. Yet, the development of drugs regulating c-Myc activity has been challenging. To facilitate the identification of c-Myc inhibitors, we developed a molecular imaging sensor-based high-throughput screening (HTS) system. This system uses a cell-based assay to detect c-Myc activation in a HTS format, which is est...

This paper presents experimental and simulation results of a screening current induced magnetic field (SCF) in a high temperature superconductor (HTS) insert that constitutes a low-/high-temperature superconductor (LTS/HTS) NMR magnet. In this experiment, the HTS insert, a stack of 50 double-pancake coils, each wound with Bi2223 tape, was operated at 77 K. A screening current was induced in the...

Intimal hyperplasia is the cause of the recurrent occlusive vascular disease (restenosis). Drugs currently used to treat restenosis effectively inhibit smooth muscle cell (SMC) proliferation, but also inhibit the growth of the protective luminal endothelial cell (EC) lining, leading to thrombosis. To identify compounds that selectively inhibit SMC versus EC proliferation, we have developed a hi...

The PhoP regulon, a two-component regulatory system is a well-studied system of Salmonella enterica serotype typhi and has proved to play a crucial role in the pathophysiology of typhoid as well as the intercellular survival of the bacterium within host macrophages. The absence of PhoP regulon in the human system makes regulatory proteins of PhoP regulon for target specific for future drug disc...

Several hundred PDZ (postsynaptic density-95, Drosophila disks-large, ZO-1) domain-containing proteins have been identified in the human genome. PDZ domains play a critical role in organization and function of cellular signaling pathways. Thus, small molecule inhibitors of PDZ domain association with their targets have wide potential applications as research and therapeutic agents. PDZ domains ...

Initial leads for drug development often originate from high-throughput screening (HTS), where hundreds of thousands of compounds are tested for biological activity. As the number of both targets for screening and compounds available for screening increase, there is a need to consider methods for making this process more efficient. One approach is to screen sequentially, whereby a relatively sm...

MDM2 and XIAP are mutually regulated. Binding of MDM2 RING protein to the IRES region on XIAP mRNA results in MDM2 protein stabilization and enhanced XIAP translation. In this study, we developed a protein-RNA fluorescence polarization (FP) assay for high-throughput screening (HTS) of chemical libraries. Our FP-HTS identified eight inhibitors that blocked the MDM2 protein-XIAP RNA interaction, ...