Combinatorial Chemistry & High Throughput Screening - Volume 11, Issue 3, 2008

The last two decades have seen the rapid and extensive adoption of an increasingly diverse portfolio of automated high throughput technologies by the pharmaceutical and biotechnology industries. Such approaches are now established as a ubiquitous and integral component of modern drug discovery. From the inception of high throughput screening up until the early 90s', such techniques were predominantly applied to facilit Read More

High throughput technologies have the potential to affect all aspects of drug discovery. Considerable attention is paid to high throughput screening (HTS) for small molecule lead compounds. The identification of the targets that enter those HTS campaigns had been driven by basic research until the advent of genomics level data acquisition such as sequencing and gene expression microarrays. Large-scale profiling approaches (e Read More

Ion channels are a large superfamily of membrane proteins that pass ions across membranes. They are critical to diverse physiological functions in both excitable and nonexcitable cells and underlie many diseases. As a result, they are an important target class which is proven to be highly “druggable”. However, for high throughput screening (HTS), ion channels are historically difficult as a target class due to their unique m Read More

GPCRs had significant representation in the drug discovery portfolios of most major commercial drug discovery organizations for many years. This is due in part to the diverse biological roles mediated by GPCRs as a class, as well as the empirical discovery that they have proven relatively tractable to the development of small molecule therapeutics. Publication of the human genome sequence in 2001 confirmed GPCRs as t Read More

High-Content Analysis (HCA) has developed into an established tool and is used in a wide range of academic laboratories and pharmaceutical research groups. HCA is now routinely proving to be effective in providing functionally relevant results. It is essential to select the appropriate HCA application with regard to the targeted compound's cellular function. The cellular impact and compound specificity as revealed by HCA a Read More

Small molecule high-throughput screening in drug discovery today is dominated by techniques which are dependent upon artificial labels or reporter systems. While effective, these approaches can be affected by certain experimental limitations, such as conformational restrictions imposed by the selected label or compound fluorescence/quenching. Label-free approaches potentially address many of these issues by Read More

High throughput screening (HTS) for complex diseases is challenging. This stems from the fact that complex phenotypes are difficult to adapt to rapid, high throughput assays. We describe the recent development of high throughput and high-content screens (HCS) for neurodegenerative diseases, with a focus on inherited neurodegenerative disorders, such as Huntington's disease. We describe, among others, HTS assays Read More

High throughput screening (HTS), an industrial effort to leverage developments in the areas of modern robotics, data analysis and control software, liquid handling devices, and sensitive detectors, has played a pivotal role in the drug discovery process, allowing researchers to efficiently screen millions of compounds to identify tractable small molecule modulators of a given biological process or disease state and advance them i Read More

With the increase in the numbers of molecules synthesized in a typical drug discovery program, as well as the large amount of information utilized in the selection of a drug candidate, there is a need for a plethora of drug metabolism and pharmacokinetic (DMPK) information to be regularly generated in discovery. Over the past decade, many in vitro, and even in vivo, DMPK screens have been developed and routinely deploy Read More

Dr. Holger Wesche is a Principal Scientist at Amgen Inc. in South San Francisco (formerly Tularik), where he has been working for the past 10 years. His group is involved in the identification and validation of novel targets for pharmaceutical intervention. Dr. Wesche's lab also works on assay development for HTS and SAR support for development candidates. His research focus is the mechanism of signal transduction and gen Read More