Ryanodine receptors (RyR) are intracellular calcium (Ca2+) release channels on the sarcoplasmic reticulum of skeletal and cardiac muscles that play a central role in excitation-contraction coupling. Genetic mutations or posttranslational modifications RyR causes hyperactivation channel, leading to various muscle heart diseases. Currently, no specific treatments exist for most RyR-associated Rec...

Large-scale screening of multiple compound libraries and combinatorial libraries for pharmacological activity is one of the novel approaches of the modern drug discovery process. The application of isozyme-specific high-throughput screening (HTS) assays for characterizing the interactions of potential drug candidates with major human drug-metabolizing cytochrome p450 enzymes (p450s) is newly be...

Phenotypic drug discovery requires billions of cells for high-throughput screening (HTS) campaigns. Because up to several million different small molecules will be tested in a single HTS campaign, even small variability within the cell populations for screening could easily invalidate an entire campaign. Neurodegenerative assays are particularly challenging because neurons are post-mitotic and ...

Microbial secondary metabolites represent a rich, chemically-diverse source of bioactive compounds that have been exploited for applications in human medicine, agriculture, and industry [1-3]. Natural product fermentation bioprocesses have remained an important tool in efforts to acquire chemical diversity in bioactive compound libraries for lead generation [4]. In recent years, natural product...

High-throughput screening (HTS) is an efficient technology for drug discovery. It allows for screening of more than 100,000 compounds a day per screen and requires effective procedures for quality control. The authors have developed a method for evaluating a background surface of an HTS assay; it can be used to correct raw HTS data. This correction is necessary to take into account systematic e...

High-throughput screening (HTS) strategies and protocols have undergone significant development in the last decade. It is now possible to screen hundreds of thousands of compounds, each exploring multiple biological phenotypes and parameters, against various cell lines or model systems in a single setting. However, given the vast amount of data such studies generate, the fact that they use mult...

Novel technologies that include recombinant pathogens and rapid detection methods are contributing to the development of drugs for neglected diseases. Recently, the results from the first high throughput screening (HTS) to test compounds for activity against Trypanosoma cruzi trypomastigote infection of host cells were reported. We have selected 23 compounds from the hits of this HTS, which wer...

The leukocyte-specific integrin CD11b/CD18 plays a key role in the biological function of these cells and represents a validated therapeutic target for inflammatory diseases. Currently, the low affinity interaction between CD11b/CD18 integrin and its respective ligand poses a challenge in the development of cell-based adhesion assays for the high-throughput screening (HTS) environment. Here the...

High-throughput screening (HTS) of chemical libraries is often used for the unbiased identification of compounds interacting with G protein-coupled receptors (GPCRs), the largest family of therapeutic targets. However, current HTS methods require removing GPCRs from their native environment, which modifies their pharmacodynamic properties and biases the screen toward false positive hits. Here, ...

Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities...