Applications  Technologies Map  Finding guide to terms in these glossaries  Site Map
Related glossaries include Applications: Drug Discovery & development  DrugTargets
Technologies: Combinatorial libraries & synthesis glossary, Labels, Signaling & Detection Microarrays, Molecular Imaging  

The National Institutes of Health (NIH) is committed to a major effort to broaden access to high-throughput screening (HTS) technologies, and the information produced by these approaches, for researchers in academia, government, and non-profit institutions. The public sector has not yet taken advantage of the considerable potential of HTS to advance the understanding of biology and disease mechanisms because access by academic scientists to automated screening facilities and diverse compound libraries is very limited. Solicitation of Assays for High Throughput Screening (HTS) in the Molecular Libraries Screening Centers Network (MLSCN), NIH  PAR-05-060, March 1, 2005 http://grants.nih.gov/grants/guide/pa-files/PAR-05-060.html 

analysis, molecular - innovative: Molecular analysis technologies of interest [to the National Cancer Institute] include those that are entirely novel, or emerging but not currently in broad scale use, or technologies currently in use for one application or set of applications, that are being evaluated for utility for alternative applications. ... Technologies suited for this solicitation, include those that enable the: detection of alterations and instabilities of genomic DNA; measurement of expression of genes and gene products; analysis and detection of gene and or cellular products including differential expression, quantitation, post translational modification, and function of proteins; identification of exogenous infectious agents in cancer; assaying the function of major signal transduction networks involved in cancer. Additionally, technologies that will support molecular analysis in vitro, in situ, or in vivo (by imaging or other methods) are suitable. [NCI, Innovative Technologies for the Molecular Analysis of Cancer, 2001] http://otir.nci.nih.gov/tech/imat_ini.html#inno

Narrower term: high content analysis  Related terms: Cell biology glossary cellular resolution; Expression glossary molecular profiling

assay A set of operations having the object of determining the value of a quantity. In analytical chemistry, this term is synonymous with measurement. [IUPAC Compendium]

Generically a bioassay where biological activity is derived; associated with a bioactive effector molecule. Within the screening discipline, an assay will probably be robust enough and have the capacity to enable testing of up to 10,000 samples, generally with limited chemical diversity. [The precise definition of the following terms varies widely between drug discovery companies. The meanings given here are aligned with the use of the terms within the lead discovery function at GlaxoWellcome.  Martin J. Valler,  Darren Green  "Diversity screening versus focussed screening in drug discovery" Drug Discovery Today 5(7): July 2000]  

It could be argued that the rate-limiting factor in biology at the moment is not the speed of assays but devising the assays themselves; that is, establishing new and imaginative ways of measuring biological activity in vivo or in vitro and then using genetics or biochemistry to use the players - Kim Nasmyth ["Opinions on the potential of yeast biochemical genomics" in "The awesome power of yeast biochemical genomics" Trends in Genetics 16 (2): 49- 51 Feb. 2000]

Narrower terms:  Enzyme- Linked Immunosorbent Assay ELISA, force assays, primary assays, secondary and tertiary assays; bioassay, cell assays, high content assays, homogeneous assays, immunoassay, quantitative assays, sandwich assay, single cell metabolism and enzyme assays, "smart" assays;  primary assays, secondary assays; Related terms: screening

bead assays:

binding assays: See under force assays

bioassay: A procedure for determining the concentration or biological activity of a substance (e.g. vitamin, hormone, plant growth factor, antibiotic, enzyme) by measuring its effect on an organism or tissue compared with a standard preparation. [IUPAC Medicinal Chemistry]

A bioassay is a single step within a microarray experiment. There are 3 types of bioassays. A physical bioassay correspond to wet- lab microarray experimental step. A measured bioassay corresponds to a situation after feature extraction has been performed. A derived bioassay corresponds to data processing experimental steps. [MGED "bioassay"]  http://www.mged.org/Workgroups/MAGE/bioassay.html

biochemical assays: Measure how compounds bind to targeted molecules (such as receptors) or how compounds inhibit enzyme activities. CHA High- Content Analysis Market Outlook report, 2004

biochemical based assays: Topics may include but are not limited to: Protein expression, purification and optimization procedures to maximize yield, Library design and synthesis, Coupling of biochemical- based HTS with robotics, Labeling techniques, Label- free screening, Assays for challenging proteins, Novel technologies, Screening protein- protein interactions, Data mining and analysis, In silico screening , Miniaturized HTS assays, High Content Screening BIOCHEMICAL-BASED ASSAYS FOR HTS: Maximizing Quality, Efficiency and Information Content , May 13-14, 2008 • Philadelphia, PA

biomolecular screening:  Over the past 15 years, high throughput screening (HTS) of small molecules has become a mainstay in the drug discovery process both in lead discovery and lead optimization. In both HTS and routine screening to optimize lead structures, new technologies, techniques and terminology have emerged. A definitive glossary of biomolecular screening terms will be broadly useful to scientists involved in the drug discovery process. The glossary will be generated in collaboration with the Society for Biomolecular Screening. Update of 1999 Glossary of terms used in biomolecular screening Chemistry and Human Health Division (VII) IUPAC project Number: 2004-019-3-700, last update March 2005 http://www.iupac.org/projects/2004/2004-019-3-700.html

cell assays, cellular assays: Cell biology is also looking less traditional these days. Companies ... have developed live cell assays that fully automate sample handling and quantify cellular characteristics such as motility, proliferation and morphology. The ability to track the behavior of individual cells over time permits data gathering on functional behavior not available in any other kind of assay. This functional assay technology is amenable to high throughput analysis, and therefore can occupy a niche complementary to many proteomic technologies focused on identification of potential therapeutic targets. 

Can be used for drug screening ... some companies are using such assays to gain insights about target function.... assays [can also be used] to get detailed functional information 

Google = "cell assays" about 1,900  "cellular assays" about 1,130  Aug. 21, 2002

Related term: Microarrays glossary: phenotypic microarray Narrower term: live cell assays

cell-based assays: Much of last year’s event focused on the development of cells as reagents, label-free cell-based screening as well as novel approaches and technologies. Progress towards these goals will be discussed and further updates on the challenges raised will be presented. In addition, this event will be immediately followed by a separate forum on Biochemical-Based Assays for HTS.  Cell-Based Assays for HTS:  Developing Robust Reliable & Sensitive Assay Formats at the right cost,  May 12-13, 2008 • Philadelphia PA

Any of a number of assays done in living cells. In the context of high- content screening, researchers typically observe the various effects of investigational compounds on cellular activities (e.g., movement of transcription factors to the nucleus), with the aim of getting functional readouts for the compounds. Key to getting information from cell- based assays are image analysis and image- processing techniques.  CHI High- Content Analysis Market Outlook report, 2004

Google = about 2, 780 Aug. 21, 2002; about 9,780 Mar. 22, 2004

Narrower term: high throughput cell based assays  Related terms: cell assays, cellular assays

cell free screening:   

cellular screens: See cell assays, cellular assays

Google = about 51 Aug. 21, 2002; about 554 Nov 10, 2006

combinatorial libraries: Combinatorial libraries & synthesis glossary

competitive immunoassays: Rely on the competition between a labeled and unlabeled antigen for a limited number of antibody binding sites. [B. Weigl et al “Novel Immunoassay formats for integrated microfluidic circuits” SPIE  BIOS 2000]  http://www.micronics.net/spiebios2000/spie2000novelIAformats.htm

A single antibody is bound to a small molecular weight antigen of less than 10,000 kD. The antibody, at a very low concentration, binds the antigen in  the sample. Then a known concentration of antigen is labelled with a detector … All  remaining antibody sites bind the labelled antigen.  The amount of either the bound or free- labeled antigen added to the  reaction is measured at the end of the immunological binding reaction. The  percentage bound is inversely proportional to the amount of unlabeled  antigen. The antibody bound enzyme- labeled antigen is separated at the  end of the immunological binding reaction using a secondary antibody coated  microplate that specifically binds the primary antibody. The resulting signal is  inversely proportional to the amount of antigen in the sample. [Whatman Polyfiltronics, Technical Support, Archives  “An introduction to assays”] http://www.whatman.plc.uk/

Broader term: immunoassay; Related term: competitive PCR

compound validation: A process to quickly determine whether a molecule identified in a screen or assay will eventually lead to a drug. If you look at the costs of developing compounds into drugs, the most costly failures result from toxicity or pharmacokinetic liabilities rather than from their failure to act on the target. 

Related terms: Target validation glossary

Conformation-Dependent Immunoassays CDI:

counterscreens:  Investigators must develop counterscreens for their assays, with potential deselection criteria including toxicity and suppression of expression from CMV or another promoter.  Draft copy: report  Workshop on Drug Discovery for Huntington's Disease, Cambridge, MA, February 10- 11, 2001 http://www.hdfoundation.org/workshops/20010210Abstract.php 

Pharmaceutical researchers typically counterscreen candidate compounds against a limited number of related available targets, sometimes resulting in toxicity problems that involve off- target interactions with other previously unknown proteins in the family. [ActivX Technology "Activity Based Proteomics"  http://www.activx.com/technology.htm

derived bioassay: See under bioassay

diagnostics: Molecular Medicine glossary

difficult target screening: Drug targets glossary

dissociator assays: Proteomics glossary

diversity screening: The drivers behind the current ethos of large- scale diversity HTS are rooted in the desire to build an improved hit identification process, and are based on the simple model of testing everything. The key activity over the past five or so years has been scaling: taking the existing model and increasing capacity by application of technology. [Martin J. Valler,  Darren Green  "Diversity screening versus focussed screening in drug discovery " Drug Discovery Today 5 (7) : July 2000]  

diversity oriented screening: As combinatorial chemistry matures, diversity- oriented synthetic chemists are achieving more structural complexity, tackling compounds with multiple stereocenters and complex natural product- like core structures. Recent advances in multi-component reactions and asymmetric catalysis push the frontiers of effectively populated chemical space. Structurally complex and diverse compound libraries effectively probe biological space for finding initial leads, while targeted, focused libraries enable more rapid lead optimization. Diversity Oriented Synthesis: Populating Chemical Space, Nov. 9-10, 2004, Boston MA

drug screening:

druggable genome: Drug discovery & development glossary

ELISA: SEE Enzyme- Linked Immunosorbent Assay 

Enzyme-Linked Immunosorbent Assay ELISA: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme- antibody- antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [MeSH, 1986]

focussed screening: Focussed screening is now well established as a successful hit generation strategy. With focussed screening, it should also be possible to use an assay that is more appropriate, rather than one that works well at a large scale.  [Martin J. Valler,  Darren Green  "diversity screening versus focussed screening in drug discovery " Drug Discovery Today 5 (7): July 2000] 

fragment based drug discovery:   The fragment-based approach to drug design has potential for efficient progression into clinically successful compounds.  Topic List may include  • Designing Improved Fragment Libraries, • Generic vs Directed Libraries, • Library Application, • Advances to Improve Initial Screen Technology, • Novel Approaches to Characterization and Optimization of Leads, • Biological Assay Screens, • Clinical Case Studies.  Fragment based drug design, May 14-15, 2007, La Jolla,  CA

functional bioassays:  Here, the concept of an array of 'functional' bioassays is presented which has ultimately been developed from the classical tool of mode of action diagnosis by symptoms. These bioassays are designed to differentiate between the distinct responses of the multiple organization units (plant, tissue, meristematic cell, organelle), developmental stages, types of metabolism (phototrophic, heterotrophic) and physiological processes in the plant organism. The response pattern to a herbicide can be viewed as the end result of changes induced in the molecular and biochemical process chain and should be diagnostic of its physiological mode of action.  K. Grossmann, What it takes to get a herbicide's mode of action. Physionomics, a classical approach in a new complexion, Pest Manag Sci.  Jan 20, 2005 

Related term: physionomics 

GLP Good Laboratory Practice: Writing SOPs, Validation and qualification, dealing with regulations, outsourcing and international perspectives Guide to GLP Comprehensive & Practical Aug 22-23, 2007 Cambridge MA

High Content Analysis HCA:  High content analysis (HCA) is the convergence between cell-based assays, high-resolution fluorescence imaging, automation and advanced image processing and analysis software. It has been widely adopted in the pharmaceutical and biotech industries for target identification and validation and as secondary screens to reveal potential toxicities or to elucidate a drug’s mechanism of action. In particular, HCA has made inroads into R&D applications where high throughput screening (HTS) has proven inadequate, such as measuring multiple biological pathways simultaneously, or revealing off-target drug effects. HCA has stepped into this void by demonstrating how particular proteins are affected by the application of a molecule to the cell line of interest. High Content Analysis, Technologies, Applications, Market Analysis, InsightPharma Reports, 2007 

Over the four years of organizing the High Content Analysis meeting, we have observed the technology mature and its adoption spread into many areas of compound screening/evaluation and functional analysis. This year’s meeting will focus on the next steps of technology development, including new assays and reagents, more advanced data analysis and archiving, and higher capacity instrumentation.  High Content Analysis January 14-17, 2008 • San Francisco, California

Many processes can be studied using HCA, including intracellular translocation of proteins; movement of proteins in response to activation of a receptor or a cellular pathway; and protein co-localization. Such studies have enormous potential to streamline drug discovery.  Jim Kling, High Content Analysis BioIT World 6 (9): 26- 30 Nov 2007  http://www.bio-itworld.com/issues/2007/nov/cover-story-high-content-analysis/ 

Google = about 420 July 14, 2004, about 9,860 Aug. 22, 2005; about 42,000 May 15, 2006; about 75,100 Nov 10, 2006; about 65,100 Apr 6, 2007, about 31,700 Sept 10, 2007

Related/equivalent terms: high content assays,  high content screening

high content assays:  Google = about 164 July 14, 2004, about 381 Aug. 22, 2005; about 654 Nov 10, 2006, about 784 Sept 10, 2007

High content cellular analysis: Google = about 122 Aug. 6, 2004, about 192 Aug. 22, 2005; about 329 Nov 10, 2006, ab out 1,090 Sept 10, 2007

high-content screening HCS: The area of High Content Screening is moving at a very rapid pace. It is hard to keep up. The purpose of this website is to provide a forum for those working in this field, a mechanism for exchange of information, an opportunity to develop educational tools and a facility to create training opportunities. Purdue Univ. Cytometry Laboratories   http://www.cyto.purdue.edu/HCS/ 

Google = about 4,100 July 14, 2004, about 15,800 Aug. 22, 2005; about 124,000 Nov 10, 2006; about 239,000 Sept 10, 2007

Related/equivalent term: high content analysis

high throughput microscopy: Microscopy glossary

High Throughput Screening HTS: Process for rapid assessment of the activity of samples from a combinatorial library or other compound collection, often by running parallel assays in plates of 96 or more wells. [IUPAC Combinatorial Chemistry] 

Traditionally describes the running of a large-scale assay campaign looking at the effects of a large number of compounds on a biological target. CHI High- Content Analysis Market Outlook report, 2004

Google = about 260,000 Aug. 22, 2005; about 1, 050, 000 Nov 10, 2006

Broader term: screening   Narrower term: ultra high throughput screening
Related terms: high content analysis, high content screening, throughput

hit:  Library component whose activity exceeds a predefined, statistically relevant threshold. [IUPAC Combinatorial Chemistry] 

A molecule with robust dose­ response activity in a primary screen and known, confirmed structure. The output of most screening. [The precise definition of the following terms varies widely between drug discovery companies. The meanings given here are aligned with the use of the terms within the lead discovery function at GlaxoWellcome.  Martin J. Valler,  Darren Green  "Diversity screening versus focussed screening in drug discovery" Drug Discovery Today 5(7): July 2000] 

Related terms: High Throughput Screening HTS, hit optimization library, lead discovery, screening. Narrower term: integrated hit identification, progressible hit

hit optimization library: Combinatorial Libraries & synthesis 

hit to lead: Reaching the next rung in hit-to-lead and lead optimization poses persistent challenges in the quest for successful drugs. As costs escalate, innovative approaches are needed to develop more efficient processes that lead to optimized compounds. With the help of emerging technologies – software, modeling, automation – Hit to Lead to Optimization can progress into a new age of drug discovery. What assays work well for your group? What approaches have you initiated that have streamlined processes and improved timelines? What advice can you share about new ways to achieve novel compounds with desired qualities? We will also be discussing software – what your group uses and how you use it. The Spotlight on Software will include brief presentations on software programs followed by discussions from end-users. We’ll also take a look at outsourcing and collaborating, including how to find top-notch vendors and CROs, and develop relationships.   Hit-to-Lead Optimization  June 12-13, 2007 • Philadelphia, PA  Related term: lead optimization

homogeneous assay: These assays require no separation steps. Pipette, incubate, and measure  are the only steps required. The reactions occur completely in solution  generally without beads or solid phase attachments to interfere with low  affinity interactions. Homogeneous assay methods are essential for the throughputs required in drug discovery and for assay miniaturisation. In any homogeneous assay, all the components of the assay are present during  measurement. The elimination of separation steps is the major advantage of  these assays, but this presents difficulties because of non- specific  measurement of the assay constituents. Whatman Polyfiltronics. Technical Support, Archives  “An introduction to assays” http://www.whatman.plc.uk/

image analysis/image processing: In the context of high- content screening, these efforts involve drawing conclusions from image- based data, typically from living cells that have been exposed to compounds of interest. Analyzing such images can be challenging for many reasons, including the transient nature of cellular events and the fact that image- processing algorithms are still not robust enough for certain important applications (e.g., pattern recognition).  

Related terms: Molecular Imaging glossary

immunoassay: A ligand- binding assay that uses a specific antigen or antibody, capable of binding to the analyte, to identify and quantify substances. The antibody can be linked to a radiosotope (radioimmunoassay, RIA), or to an enzyme which catalyses an easily monitored reaction (enzyme- linked immunosorbent assay, ELISA), or to a highly fluorescent compound by which the location of an antigen can be visualized (immunofluorescence). [IUPAC Compendium] 

Only method possible for  small molecular weight antigens, such as steroids, drugs, lipids, and  peptides. There are three basic components in any immunoassay, the  antigen to be detected and/or quantified, a specific antibody to this antigen,  and a system to measure the amount of the antigen in the sample. The  separation at the end of the immunological reaction uses a microplate. [Whatman Polyfiltronics. Archives “An introduction to assays”] http://www.whatman.plc.uk/

Introduction to Immunoassays, Abbott Diagnostics http://www.abbottdiagnostics.com/Science/pdf/learning_immunoassay_01.pdf 

Narrower term: competitive immunoassay Related term: ELISA

immunometric assay: See  sandwich assay

lead: A representative of a compound series with sufficient potential (as measured by potency, selectivity, pharmacokinetics, physicochemical properties, absence of toxicity and novelty) to progress to a full drug development programme.  [The precise definition of the following terms varies widely between drug discovery companies. The meanings given here are aligned with the use of the terms within the lead discovery function at GlaxoWellcome.  Martin J. Valler,  Darren Green  "Diversity screening versus focussed screening in drug discovery " Drug Discovery Today 5(7): July 2000]  

Related term: hit

lead discovery: The process of identifying active new chemical entities, which by subsequent modification may be transformed into a clinically useful drug. [IUPAC Medicinal Chemistry] 

Related terms: drug discovery, hit, lead generation, lead discovery library, lead optimization, screen 

lead discovery library: Combinatorial Libraries & synthesis 

lead generation: Strategies developed to identify compounds which possess a desired but non- optimized biological activity. [IUPAC Medicinal Chemistry]  

Related terms: drug development, hit, lead discovery, lead optimization

lead hopping:   Tripos http://www.iptonline.com/articles/public/IPTFIVE46NP.pdf 

Related terms:  Chemistry glossary  scaffold hopping  Drug targets glossary target hopping

lead identification: Once the therapeutic target has been identified, scientists must then find one or more leads (e.g., chemical compounds or molecules) that interact with the therapeutic target so as to induce the desired therapeutic effect.  Lifesciences Montreal, Discovery of a New Drug http://www.montrealinternational.com/sciences/drug/discovery-lead-id.html 

lead-like: Intrinsically, lead-likeness and drug-likeness are the descriptors of potency and selectivity, but also absorption, distribution, metabolism, toxicity, and scalability. Until now, these parameters were optimized sequentially, but nowadays it is believed that these parameters should be optimized simultaneously. Thierry Langer, G Wolber, Virtual combinatorial chemistry and in silico screening, Pure and Applied Chemistry 76 (5): 991– 996 , 2004 http://www.iupac.org/publications/pac/2004/pdf/7605x0991.pdf 

lead optimization: The synthetic modification of a biologically active compound, to fulfill all stereoelectronic, physicochemical, pharmacokinetic and toxicologic required for clinical usefulness. [IUPAC Medicinal Chemistry] 

Designing molecules with specific desirable attributes is a science that continues to evolve in modern drug discovery. Maximizing potency, selectivity and specificity while minimizing toxicity and off-target effects is the challenge. This meeting will cover some of the novel approaches being taken across the industry to meet the challenges of optimizing a lead and progressing a compound forward. Topics given special emphasis will include; new analytical strategies in studying drug metabolism and profiling of metabolites, drug-drug interaction and screening for CYP inhibition, recent updates of drug transporters and an analysis of the power of computational approaches such as lead hopping and core swapping. World Pharmaceutical Congress Novel Approaches to Lead Optimization May 12- 14, 2008

Related terms: hit to lead

Related terms: drug development;  Pharmacogenomics glossary ADME, toxicogenomics; Drug discovery & development prototype  Narrower term: parallel optimization

lead prioritization: One of the major steps in lead prioritization is an assessment of compound binding to plasma proteins, because it affects both the pharmacokinetics and pharmacodynamics of the compound in vivo.  Development of a high throughput equilibrium dialysis method , Ilona Kariv, Hong Cao, Kevin R. Oldenburg, J. Pharm. Sci. 90( 5) : 580- 587, 200 DOI: 10.1002/1520-6017(200105)90:5<580::AID-JPS1014>3.0.CO%3B2-4   AAPS Pharmaceutica http://www.aapspharmaceutica.com/search/view.asp?ID=4798 

lead selection: See lead discovery

lead validation: With no shortage of drug targets, increasing emphasis is being placed on lead validation. One key challenge is developing high throughput screens. 

Related term: target validation.

live cell assays:  Can be used to obtain functional information on a wide variety of cellular effects, including apoptosis, proliferation, differentiation, migration and protein secretion. Enables a better understanding of protein functionality in normal and diseased states. 

massively parallel: Many (assays or other procedures) at once.

Related term: Gene amplification & PCR multiplexing

measured bioassay: See under bioassay

medicinal chemistry: Drug discovery & development

microplate, microplate reader, microtiter plate, microtitre plate Assays & drug screening

microplate reader: Created from the tube spectrophotometer designs of the 1970s to save precious antibody samples. At first clumsy and inaccurate, absorbance microplate readers have evolved to pack unbelievable power and precision, replacing cuvette spectrophotometers for most multisample applications.¹ Continuous improvement is enhancing the classic designs to embrace the world of high- throughput (HT) screening and to allow complete analytical automation.² To handle the HT range (more than 10 microplates a day or 1,000 assays), many instruments now allow robotic handling of plates "stacked" in accessory plate handlers.  [Jorge D. Cortese " Well Read: Technological improvements are pushing microplate readers into the 21st century's high-speed, computerized world" Scientist 14 (19): 24, Oct. 2, 2000]  http://www.the-scientist.com/yr2000/oct/profile_001002.html 

microtiter plate, microtitre plate: Sample holding device used in combinatorial chemistry and high throughput screening for cloning of PCR products and construction of cDNA libraries in expression vectors. Comes in 96, 384, 1536 and 3456- well formats. Related term: sample

Profile of specialty microwell plates, Scientist 13 (19): 16 Sept. 27, 1999 http://www.the-scientist.com/yr1999/sept/profile1_990927.html  

molecular libraries screening instrumentation:  Libraries & synthesis

multiplex assays: This report examines the evolution of multiplex assay technologies and evaluates the competitive picture, growth trends, and deal-making activities in this dynamic and rapidly growing market. Insight Pharma Reports, Multiplex assays, technologies, applications and markets, 2006 http://www.insightpharmareports.com/reports/2006/63_Multiplex/overview.asp 

multiwell plate: See microtiter plate, microtitre plate.

organotypic:  Biomaterials & bioengineering

phenotypic screening: The systematic classification and characterization of phenotypes is essential for ultimately mapping the genes responsible for normal and abnormal development and physiology. In any search for mutations or altered functional expression, identification depends on phenotypic screening and its ability to detect variation from normal. The challenge is to develop efficient, systematic and comprehensive phenotypic screening procedures and tools that will permit comparison between laboratories, temporally, and between different strains of mice. This is a necessary step before utilizing chemical or other mutagenesis methods to produce large numbers of mutant mice for the investigation of normal and abnormal development and physiology. ... a primary focus of this program is the development of high throughput phenotyping assays or tests that could efficiently, rapidly, and systematically be used to screen anywhere from 5,000 to 20,000 mice per year for alterations in cardiovascular, pulmonary, hematologic or sleep physiology. This could include, but not be limited to, biochemical surrogate markers, noninvasive imaging modalities, microarray analysis, or indicator screens. Another goal is to develop new phenotyping techniques or methods for heart, lung, blood, and sleep disorders that would accelerate the emergence of new concepts and improve our understanding of structural, metabolic, and functional relationships in cardiopulmonary, and blood systems.  Development of mouse phenotypic screens for heart, lung, and blood diseases, National Heart, Lung and Blood Institute, NIH, US, Apr. 13, 1999, Request for Application http://grants1.nih.gov/grants/guide/rfa-files/RFA-HL-99-010.html

physical bioassay: See under bioassay

primary assay: Assays of drugs done on a single drug  target or small groups of targets 

primary screening:   Primary screening, which is higher throughput than secondary screening, typically seeks to identify which compounds bind to targets of interest, to what degree of affinity. In primary screens researchers may seek to determine what compounds bind to and inhibit targets of interest. CHI High- Content Analysis Market Outlook report, 2004 

progressible hit: A representative of a compound series with activity via an acceptable mechanism of action and some limited structure­ activity relationship. The precise definition of the following terms varies widely between drug discovery companies. The meanings given here are aligned with the use of the terms within the lead discovery function at GlaxoWellcome.  Martin J. Valler,  Darren Green  Diversity screening versus focussed screening in drug discovery " Drug Discovery Today 5(7): July 2000]  

Related term: Combinatorial libraries & synthesis  chemistry space

random screening: A staple of the pharmaceutical industry for many years. Now largely replaced by varying combination of combinatorial chemistry and/or rational drug design.  

Related terms: diversity screening, focussed screening Broader terms: screen, screening

sandwich assay: The antigen is "sandwiched"  between the two antibodies, one is attached to the solid phase, and the  other is labelled with an enzyme. The amount of solid phase antibody and  enzyme conjugated antibody are in a higher proportion than the amount of  antigen in the sample. The result is an assay that produces a signal that is  proportional to the amount of antigen in solution. [Whatman Polyfiltronics. Technical Support, Archives  “An introduction to assays”] http://www.whatman.plc.uk/

screen: An optimized, streamlined assay format with characterized robustness to diverse chemical types and conditions such that testing of 10,000 samples is both feasible and cost effective. The spectrum of low- throughput screening (10,000­ 50,000 assay points) medium- throughput screening (50,000­100,000 data points) and high- throughput screening (100,000­ 500,000 data points) can be defined. The scale of implementation of a given screen is greatly influenced by format, application of technology (e.g. automation), time and resource constraints. [The precise definition of the[se] terms varies widely between drug discovery companies. The meanings given here are aligned with the use of the terms within the lead discovery function at GlaxoWellcome.  Martin J. Valler,  Darren Green  "Diversity screening versus focussed screening in drug discovery " Drug Discovery Today 5(7): July 2000] 

Related term: screening. 

screening: Pharmacological or toxicological screening consists of a specified set of procedures to which a series of  compounds is subjected to characterize pharmacological and toxicological properties and to establish dose- effect and dose- response relationships. [IUPAC Tox]

The use of in vitro biochemical assays, or tests, to detect compounds which modulate the activity of a target (i.e., enzyme inhibitors, receptor agonists or antagonists). [Oxford Molecular]  

While drug screening is often talked about in the context of achieving hits, it is useful to note that the Oxford English Dictionary definition of screening specifies that this is "esp. for the detection of unwanted attributes or objects".  

Narrower terms: diversity screening, focussed screening, HTS High Throughput Screening, synthetic lethal screening, Ultra High Throughput Screening UHTS; Drug targets target screening  Not the same as screening in Molecular Medicine Related terms: assay, I.R. Thermography 

secondary assays (and tertiary assays): Undertaken after primary screening has identified "hit" compounds against drug  targets, are more complicated - and time-consuming - tests of a drug and include ADME/Tox (absorption, distribution, metabolism, excretion/toxicology) studies (e.g., done on mice or rats). Test a drug against more than one target, complicated and time- consuming, so they have not been considered practical for use in very early drug development.... . The secondary and tertiary assays tell you more biology. ...Typically, secondary and tertiary assays are more comprehensive, but they also take longer, and they are more complex and less reproducible. 

secondary screening:  Secondary screening, which is lower throughput than primary screening, seeks to provide more detailed information about compounds than just their binding affinity. For example, secondary screens may shed light on mechanism of action and other parameters. CHI High- Content Analysis Market Outlook report, 2004   

As the primary screening technologies are becoming increasingly automated and high-throughput, the drug discovery bottleneck is shifting downstream towards secondary screening and lead optimization. This is the area where researchers had the most experience with High Content Screening. The high-content cellular information on lead specificity, bioavailability, and ADME/Tox allows researchers to prioritize leads with more confidence and impact the bottom line by reducing late- stage attrition.

single cell metabolism & enzyme assays: Ultrasensitivity

small molecule screening:  The basic goal of small- molecule screening is the identification of chemically 'interesting' starting points for elaboration towards a drug. A number of innovative approaches for pursuing this goal have evolved, and the right approach is dictated by the target class being pursued and the capabilities of the organization involved. A recent trend in high- throughput screening has been to place less emphasis on the number of data points that can be produced, and to focus instead on the quality of the data obtained.  Walters WP, Namchuk M., Designing screens: how to make your hits a hit. Nature Reviews Drug Discovery 2003 Apr;2(4): 259- 266 

"smart" assays: May be operationally defined as a screening system that by its very operation conveys information about new chemistry or biology of "hits" in the system. For example, assays of interest to promote may couple the use of a cloned and expressed target protein or a nucleic acid sequence in tandem with a chemical or biosynthetic process that generates molecules for further study. Alternatively, the use of genetically definable yet underexplored organisms such as yeast, Drosophila, or C. elegans, production of expression vectors that may operate only in the presence of a compound with the desired properties, development of detection techniques based on novel patterns of molecular recognition, or strategies that require the operation of a particular molecular target to be a basis for detection would all examples. [NCI, CANCER DRUG DISCOVERY: DIVERSITY GENERATION AND SMART ASSAYS, RFA: CA-97-006, May 9, 1997] http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-97-006.html

Structure- Based Design (SBD): Has been in use within the pharmaceutical industry for over twenty-five years. Given the multi-disciplinary nature of drug discovery and development, SBD can hardly be the unique success factor. However, SBD is playing an increasingly important role. SBD of compound properties are still developing and growing in acceptance. In this program, we wish to highlight some recent breakthroughs and successes using SBD, including the accompanying interest in ligand-based design. We especially seek presentations of recent breakthroughs or "unpublished work" in the following areas: Discoveries "leading to development candidates" that can be shown. The "Med Chem" perspective- property optimization in parallel to SBD. Considerations of physicochemical compound properties. Considerations of in vitro versus in vivo pharmacological compound properties. The computational or structural viewpoint, Computational or structural methodology. Ligand-Based Design. The diverse roles of water in ligand binding to targets. Ligand design including solvents. Biophysical approaches including MS, SPR, X-ray Crystallography, NMR, Homology Models, Virtual Screening, QSAR. How to cope with structural flexibility of the target How to cope with selectivity issues (e.g. kinases, GPCR’s...) Novel targets and the validations of the targets Structure-Based Drug Design  June 7-8, 2007 • Boston, MA

synthetic lethal screening: Functional genomics

target, target characterization,  target discovery: Drug targets

target discovery in silico: In silico & molecular modeling

target validation, target validation technologies: Drug targets

tertiary assays: See secondary assays (and tertiary assays)

throughput: Output or production, rate at which something can be processed.  

Ultra High Throughput Screening uHTS: Just how fast is UHTS now?

Google = about 6,250 Aug. 22, 2005; about 32,500 Nov 10, 2006 uHTS about 35,400 Nov 10, 2006

Broader term: HTS High Throughput Screening

tissue engineering: Biomaterials & Bioengineering

tissue microdissection: Cells & cell biology

tissue models: Biomaterials

Related term: organotypic

toxicity testing: An important part of the drug- lead- optimization process in which investigational compounds are tested for their potential to cause side effects. CHA, Cambridge Healthtech Advisors Model Animal Systems: Emerging Applications and Commercial Opportunities in Drug Discovery and Development, report, 2004

Both animal models and cellular assays are utilized. 

Related terms: Drug safety & pharmacovigilance

Ultra High Throughput Screening (uHTS) : A screening rate of  100,000 assays per day. [IUPAC Combinatorial Chemistry] 

Narrower term: cell- based uHTS; Broader term: High Throughput Screening HTS

virtual screening: In silico & molecular modeling

Bibliography
Insight Pharma  GPCRs: Mining the Richest Vein in Drug Discovery report, 2003 
High Content Analysis, Technologies, Applications, Market Analysis,  InsightPharma Reports, 2007 

Alpha glossary index
How to look for other unfamiliar  terms

IUPAC is working on a Glossary of terms in Biomolecular Screening http://www.iupac.org/projects/2004/2004-019-3-700.html Number: 2004-019-3-700 

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.