BACKGROUND Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput ...

Abstract Pathological conditions caused by reduced dosage of a gene, such as gene haploinsufficiency, can potentially be reverted by enhancing the expression of the functional allele. In practice, low specificity of therapeutic agents, or their toxicity reduces their clinical applicability. Here, we have used a high throughput screening (HTS) approach to identify molecules capable of increasing...

As a partner for the DOE Metal Hydride Center of Excellence (MHCoE), GE Global Research in Niskayuna, NY developed a robust approach for metal hydride discovery as schematically shown in Figure 1. The approach is used on a daily basis at GE and it has streamlined the metal hydride discovery process. Our research allows us to investigate large numbers of compositions simultaneously, quickly scre...

Identifying the binding targets of small molecules is an essential process in drug discovery and development. The two conventional approaches include high throughput screening (HTS) and computational structural docking. HTS suffers from its expensive cost and time-consuming procedure, while the computational methods reply on simplifying assumptions that often leads to less accurate results. In ...

Fluorometric imaging plate reader (FLIPR) membrane potential dyes (FMP-Red-Dye and FMP-Blue-Dye) were evaluated for the detection of compounds acting either as positive allosteric modulators or agonists on the GABAA receptor (GABAAR). A stable HEK293 cell line with constitutive expression of the rat GABAAR α1, β2, and γ2 genes was used to establish a functional high-throughput screening (HTS) a...

BACKGROUND Leishmania species are parasitic protozoa that have a tightly controlled cell cycle, regulated by cyclin-dependent kinases (CDKs). Cdc2-related kinase 3 (CRK3), an essential CDK in Leishmania and functional orthologue of human CDK1, can form an active protein kinase complex with Leishmania cyclins CYCA and CYC6. Here we describe the identification and synthesis of specific small mole...

Over the last 10 years, protein-protein interactions (PPIs) have shown increasing potential as new therapeutic targets. As a consequence, PPIs are today the most screened target class in high-throughput screening (HTS). The development of broad chemical libraries dedicated to these particular targets is essential; however, the chemical space associated with this 'high-hanging fruit' is still un...

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a mycophagous and phytophagous pathogen responsible for the current widespread epidemic of the pine wilt disease, which has become a major threat to pine forests throughout the world. Despite the availability of several preventive trunk-injection agents, no therapeutic trunk-injection agent for eradication of PWN currently exists. In t...

Ideally, a team of biologists, medicinal chemists and information specialists will evaluate the hits from high throughput screening. In practice, it often falls to nonmedicinal chemists to make the initial evaluation of HTS hits. Chemical genetics and high content screening both rely on screening in cells or animals where the biological target may not be known. There is a need to place active c...

27 For screening of skin-whitening ingredients that modulate inhibition of melanogenesis, 28 tyrosinase promoter-based assay using a 3D spheroid culture technique is a beneficial tool to 29 improve the accuracy of raw material screening in cosmetics through mimicking of the in 30 vivo microenvironment. Although the advantages of high-throughput screening (HTS) are 31 widely known, there has bee...