success-story

Organophosphates are a class of highly toxic chemicals that includes many pesticides and chemical weapons. Exposure to organophosphates, either through accidents or acts of terrorism, poses a significant risk to human health and safety. Existing antidotes, in use for over 50 years, have modest efficacy and undesirable toxicities. Therefore, discovering new organophosphate antidotes is a […]

Recently, a number of chemical and drug screens using zebrafish embryos have been published. Using zebrafish dystrophin mutants, we screened a chemical library for small molecules that modulate the muscle phenotype and identified seven small molecules that influence muscle pathology in dystrophin-null zebrafish. One chemical, aminophylline, which is known to be a non-selective phosphodiesterase (PDE) […]

Heparanase is a key enzyme involved in the dissemination of metastatic cancer cells. In this study a combination of in silico techniques and experimental methods was used to identify new potential inhibitors against this target. A 3D model of heparanase was built from sequence homology and applied to the virtual screening of a library composed […]

In Gram-negative bacteria, production of the signal molecule c-di-GMP by diguanylate cyclases (DGCs) is a key trigger for biofilm formation, which, in turn, is often required for the development of chronic bacterial infections. Thus, DGCs represent interesting targets for new chemotherapeutic drugs with anti-biofilm activity. We searched for inhibitors of the WspR protein, a Pseudomonas […]

Oculopharyngeal muscular dystrophy (OPMD) is a late onset disease which affects specific muscles. No pharmacological treatments are currently available for OPMD. In recent years, genetically tractable models of OPMD-Drosophila and Caenorhabditis elegans-have been generated. Although these models have not yet been used for large-scale primary drug screening, they have been very useful in candidate approaches […]

The lysine acetyltransferase (KAT) Rtt109 forms a complex with Vps75 and catalyzes the acetylation of histone H3 lysine 56 (H3K56ac) in the Asf1-H3-H4 complex. Rtt109 and H3K56ac are vital for replication-coupled nucleosome assembly and genotoxic resistance in yeast and pathogenic fungal species such as Candida albicans. Remarkably, sequence homologs of Rtt109 are absent in humans. […]

The synthesis of ribosomes is an essential process, which is aided by a variety of trans-acting factors in bacteria. Among these is a group of GTPases essential for bacterial viability and emerging as promising targets for new antibacterial agents. Herein, we describe a robust high-throughput screening process for inhibitors of one such GTPase, the Escherichia […]

The prominent role of Ca2+ in cell physiology is mediated by a whole set of proteins involved in Ca2+-signal generation, deciphering and arrest. Among these intracellular proteins, calmodulin (CaM) known as a prototypical calcium sensor, serves as a ubiquitous carrier of the intracellular calcium signal in all eukaryotic cell types. CaM is assumed to be […]

The kinase MEKK2 (MAP3K2) has recently been implicated in tumor growth and metastasis. Thus, selective inhibition of MEKK2 may be a novel strategy for cancer therapy. To identify inhibitors of MEKK2 kinase activity, we have developed a novel activity assay for MEKK2 based on the discovery that recombinant purified MEKK2 has intrinsic ATPase activity. This […]

We have developed a surface plasmon resonance (SPR)-based inhibition in solution assay (ISA) to search for inhibitors of the medium affinity (KD = 0.8 μM) interaction between an E6-derived peptide (E6peptide) immobilized on the sensor and a PDZ domain (MAGI-1 PDZ1) in the mobile phase. DZ domains are widespread protein-protein interaction modules that recognize the […]