CHI’s Drug Discovery and Development Map  http://www.healthtech.com/drugdiscoverymap.asp 

Drug discovery & development Map: Finding guide to terms in these glossaries  Site Map 
Related glossaries include   Drug Safety, Pharmacovigilance & Post Marketing Surveillance    Drug targets  Pharmacogenomics  
Business  Business of biopharmaceuticals   Clinical trials, drug, device & diagnostics approvals   Finance    Pharmaceutical Intellectual property   
Informatics  Bioinformatics   Chemoinformatics   Information management & interpretation    In silico & molecular modeling 
Technologies Assays & screening   Combinatorial libraries & synthesis   Microarrays & protein chips   
Biology   Chemistry & biology    Pharmaceutical biology  

96, 384, 1536, 3456 well plates: See under microtiter/ microtitre plates.

analogue based drug discovery:  Considerable success has been achieved in the development of new drugs based on the leads provided by established drugs.  Such new drugs are often considered deprecatingly as "me-too" products.  However the book will demonstrate that it is part of the very important process where by drug action is optimized for a given therapeutic effect. IUPAC Project 2002-051-1-700 http://www.iupac.org/projects/2002/2002-051-1-700.html

Related term: drug prototypes,  Drug approvals: follow ons,  me too drugs

antibacterials: This rise in drug resistances and the need to develop novel antibiotic treatment strategies present excellent opportunities for business and research alike. Many questions need to be answered in order to develop novel therapeutics and to “stike back” against the bacterial force. Multiple versus simple targets? Small versus large Molecules? What is happening during the active uptake of antibiotics? What are the current regulatory views and changes on novel antibacterial products? What are the newest emerging resistances?  Challenge of Antibacterial Drug Development April 23- 24, 2008 • San Diego, CA

antibody therapeutics: See under protein therapeutics 

antiviral therapeutics: This report assesses the compounds, the clinical data, the companies, and the market-shifting developments in the antiviral therapeutic category. Sales of antiviral agents currently constitute 25% of the anti-infective drug market. The ability of viruses to develop resistance against drugs, coupled with sub-optimal treatment outcomes as a result of failure of patients to comply with the full course of therapy, will continue to provide the commercial and medical incentive for intense R&D activity. Insight Pharma reports, Antiviral Therapeutics: Pipelines and Competitive Dynamics, 2006 

assays: Assays & screening  

attrition:  High attrition rates in pharmaceutical R&D continue to be a challenge and ways to reduce these are increasingly required.  Narrower term: early attrition

autoimmune diseases - novel biologics: Recent approvals of biologics by the FDA turned them into very attractive therapeutics for the pharmaceutical industry. Immunomodulators are one of the most promising new therapies for autoimmune diseases such as MS, Lupus, rheumatoid arthritis and IBD and Crohn’s disease. Preliminary list of topics include fusion proteins and antibodies, humanized monoclonal antibodies for inflammatory disease. For solid or hematopoietic tumors: tumor associated antigens, antimyelin antibodies, hsp derived peptides, gene therapy, NK cells, cytokines, soluble receptors, TNF – sol rec, IL-4 (hiv) – cyt, Soluble IL receptors, Interferon alpha/ beta/ gamma, Small proteins, Recombinant cytokines, Soluble cytokine receptors, Small molecule mimetics. Novel biologics for autoimmune diseases August 23-24, 2007 • Boston, Massachusetts

automation: Automating processes is often a critical part of industrializing processes developed in the research lab.  Higher throughput, quality control and better reproducibility are part of this process.. Automation may be cheaper, particularly in the long run. 

Related terms:  Bioprocessing  LIMS, robotics

backup entities: It is important to distinguish between varieties of backup entities. The primary compound chosen for advancement is called, for our purposes, a prototype. A backup compound may be a member of the same lead series or may represent a distinct chemical scaffold or chemotype. A backup program will have a prototype addressing a different molecular target than the original prototype, and it will have a prototype compound of its own, possibly with its own backup compounds of the types described. Often, backup compounds will have been prepared before much testing has been done on a prototype. Compounds synthesized in response to some deficit of the prototype found in testing are called follow-on compounds.  Insight Pharma Reports, Backup Compound Strategies: Best Practices for Reducing Phase II Risk, 2007

Bayesian clinical forecasting: Drug approvals and clinical trials

biologics, biopharmaceutical: Drug approvals

blockbuster drugs: Business of biopharmaceuticals

blood brain barrier: Topics covered include Novel Targets Identification and Validation; Novel Delivery Strategies; Dealing with the Liability of CNS Drug Side-effects; Crossing the Blood-Brain Barrier - BBB Penetration, Pharmacokinetics and Drug Metabolism The Challenge of the Blood Brain Barrier: A Medicinal Chemistry Perspective Molecular Medicine Short course, Feb 27, San Francisco CA 

cancer diagnostics: Cancer genomics 

cardiovascular diagnostics: Molecular medicine and diagnostics

cell therapeutics, cellular therapy: Stem cells

chemical biology, chemical genetics, chemical genomics, chemical ligand studies, chemogenomics: Chemistry & biology  

clinical development, clinical trials: Drug approvals

clinical forecasting: Drug approvals and clinical trials

combination drug/diagnostic products: This report includes a quantitative survey, rendered in easy-to-scan charts, of the industry's views, plans, and current actions with regard to combination drug/diagnostic products. A review of drug/diagnostic combinations in current use … A review of existing safety and status biomarkers that are being used as diagnostics, such as a simple genotyping test to guide warfarin dosing, or molecular markers for identifying responders to Gleevec and Nexavar.  Patenting activity around combination drug/diagnostic products in cancer, neurodegenerative disease, respiratory disease, and viral infection. The current state and outlook for reimbursement of diagnostics, including a case study of Genomic Health’s Oncotype DX gene expression test for predicting the benefits of chemotherapy in newly diagnosed breast cancer patients. A model of the potential expansion of a therapeutic market generated by incremental improvements in biomarker test sensitivity. Implications of FDA’s IVDMIA and ASR draft guidances. Insight Pharma Reports, Combination Drug/Diagnostic Products, 2007

combination products: As defined in 21 CFR § 3.2(e), the term combination product includes: 4 definitions follow...   FDA Office of Combination Products  http://www.fda.gov/oc/combination/ 

combination therapies: Today, combination products range from drug-drug combinations to drug-device combinations, such as drug-eluting stents for coronary blockages, to drug-biological products, such as monoclonal antibodies combined with a chemotherapy agent for the treatment of cancer. Each product type offers significant solutions to many of the problems plaguing healthcare. Insight Pharma Reports, Combination Therapies: Benefits and Challenges in Drug, Device and Biologicals Development, 2005 

As ever more combination therapies are applied in various areas of medicine, there is a growing need for quantitative descriptions of combination effects. While most of the scientific community has agreed on a basic standard for synergy, there is no consensus on quantifying the degree to which a combination may deviate from synergy, and no predictive models are accepted to serve as benchmarks.  This project will convene a working group, involving leading experts on combination effects, to (1) endorse the synergy criterion recommended at a recent meeting in Finland, (2) adopt standard measures of combination effect to quantify deviations from synergy, and (3) explore predictive combination-effect models for multiply-inhibited biological interaction networks. Quantifying the Effects of Compound Combinations Chemistry International 25 (4) July-Aug. 2004, http://www.iupac.org/publications/ci/2004/2604/pp5_2003-059-1-700.html

companion diagnostics: One trend in genetic diagnostics and therapeutics is to become increasingly intertwined.  Companion diagnostics identify subsets of patients who would benefit from a specific drug. 

Google = about 133 Nov. 3, 2004, about 241 Aug. 22, 2005; about 15,500 Nov 10, 2006

Related terms:  genetic diagnostics, molecular diagnostics;  /synonym? Pharmacogenomics glossary   pharmacogenomics

cytokine-based therapeutics: Topics to be covered include: Developing novel agonists, antagonists and recombinant cytokines., Developing next generation agents for improved efficacy, safety and/or delivery method , Evaluating the therapeutic potential of untapped cytokine targets, Assay development and screening, Identifying novel therapeutic targets , Clinical impact of genetic polymorphisms in cytokines and receptors, Latest technologies in cytokine research Cytokine-based Therapeutics: Cancer and Autoimmune Disease, Molecular Medicine, March 25-28, 2008, San Francisco, CA

Cytokines have drawn immense interest from the pharmaceutical industry over the last two decades. Great effort has been devoted to finding ways to reproduce their effects—or to block their activity—in the quest to create novel drugs for cancer, infectious diseases, inflammatory and immune disorders, and myelosuppression. Cytokine Therapies and Inhibitors: A Vibrant Pipeline and Active Approved Market 2007

Related term: Protein categories: cytokines

de novo design: The design of bioactive compounds by incremental construction of a ligand model within a model of the receptor or enzyme active site, the structure of which is known from X-ray or NMR data. [IUPAC Medicinal Chemistry] 

Related terms: Molecular modeling,  Pharmaceutical biology

developability: Drug 'developability' assessment has become an increasingly important addition to traditional drug efficacy and toxicity evaluations, as pharmaceutical scientists strive to accelerate drug discovery and development processes in a time- and cost-effective manner. D. Sun et. al, In vitro testing of drug absorption for drug 'developability' assessment: forming an interface between in vitro preclinical data and clinical outcome. Curr Opin Drug Discov Devel.; 7(1): 75- 85, Jan 2004

Google = about 1,730 Mar. 5, 2004; about 75,200 Nov 10, 2006

diabetes:: A worldwide epidemic of type 2 diabetes has been in progress since the mid-1980s, according to the World Health Organization. The worldwide number of diabetics was 30 million in 1985 and is projected to increase to at least 366 million by  2030. ...  Report has background for understanding the nature, epidemiology, pathobiology, and cost of diabetes. Experimental therapeutic strategies for prevention of type 1 diabetes in susceptible individuals. The pathogenesis of type 2 diabetes and its relationship to obesity. Current diagnosis and treatment modalities for diabetes, types 1 and 2 An evaluation of competitors in the diabetes market―their pipelines and specific products, alliances, therapeutic focus, and more . Assessment of novel classes of antidiabetics that include drugs introduced into the market in 2005 and 2006, as well as drugs in still newer classes now in corporate pipelines. Assessment of leading research and preclinical-stage drugs, and novel therapeutic strategies for type 2 diabetes. Assessment of agents in development for diabetic complications, including a novel unifying model for induction of microvascular complications, and a novel model for induction of macrovascular complications . The market outlook for new antidiabetic drugs.  Insight Pharma Reports, Diabetes and its Complications: Strategies to Advance Therapy and Optimize R&D. 2007

Discovery On Target October 20-24, 2008 • Boston, MA

diagnostics, molecular: Molecular Medicine and Diagnostics

disease targets: Drug Targets

docking: In silico & molecular modeling

drug: Drug approvals

Related term: Cheminformatics rules of five.  Also known as Lipinski's rules of five. 

drug design: Chemoinformatics

drug development: Process of optimizing compounds following drug  discovery. 

Related terms: attrition, hit to lead, lead optimization, lead validation

drug discovery: Pharmacologic therapeutics represent the single most important commercial product of biomedical research, and they have an unsurpassed track record of improving human health. Nevertheless, drug discovery and development is a costly, time consuming, and high risk activity. The process starts with the discovery of an agent or class of agents with particular activity. Lead compounds must then be identified, optimized, and only then tested in preclinical conditions for safety, toxicity, etc. Those agents still considered viable after such rigorous scrutiny are then brought to human subjects for clinical evaluation of a variety of aspects of the agent, including safety, effectiveness, and dosage determination.   COMPETING CONTINUATION AWARDS OF SBIR PHASE II GRANTS FOR PHARMACOLOGIC AGENTS AND DRUGS FOR MENTAL DISORDERS PA-02-173, Sept. 27, 2004, EXPIRATION DATE: October 2005 http://grants.nih.gov/grants/guide/pa-files/PA-02-173.html

Related terms: drug development, target validation

drug discovery and molecular imaging:  Molecular imaging’s core role for the pharmaceutical industry is in drug discovery and development. Pure research is already profiting from cell- based molecular imaging, which will continue to be based on fluorescence, bioluminescence, and confocal microscopy. Applications in small animal imaging, lead characterization, and lead optimization are also discussed. The insights into basic cell biology that this research is yielding today will form the basis of drug development during the second half of the decade, as the results are absorbed by the pharmaceutical industry. CHA Cambridge Healthtech Advisors, Molecular Imaging Comes of Age: Applications and Impacts in Discovery, Clinical Trials, and Medical Practice reports  

drug discovery pipeline: The process of drug development has evolved into an extremely complex procedure. The average drug takes 12 years and $270 million from initial discovery to public usage.(1) For every drug that is deemed marketable by the FDA, thousands of others are considered either unsafe or ineffective clinically. Beginning with preclinical research, new chemical entities (NCEs) are discovered in laboratories and tested in animals for safety and biological activity. If a compound is thought to be safe and effective as a chemical agent, a pharmaceutical company then submits an investigational new drug application (NDA) to the FDA. Once approved for clinical studies, a three-phase process begins where safety and efficacy are continually assessed with increased scrutiny and an increasing patient population. Approximately 70% of drugs entering clinical trials complete Phase I, 33% complete Phase II, and 27% complete Phase III. After Phase III is completed a company then submits a NDA to the FDA. Those drugs that are approved for marketing comprise an extremely small percentage of new chemical entities (NCEs) that are tested. In fact, from thousands only a handful of drugs undergo clinical studies, and even fewer receive market approval. [C. Daniel Mullins et. al. " Projections of drug approvals, patent expirations and generic entry from 2000 to 2004" report prepared for the Dept. of Health and Human Services' Conference on Pharmaceutical Pricing Practices, Utilization and Costs August 8- 9, 2000, Washington DC, US] http://aspe.hhs.gov/health/reports/Drug-papers/Mullins-Palumbo%20paper-final.htm

A pipeline is best defined as what the company potentially has to offer for a product. Key word: potentially. It s not a guarantee that whatever it is will actually succeed, something many investors forget when they run screaming towards the latest trends with arms extended, green bills in hand. The pipeline is the umbrella term for anything under construction, or as some people like to say -- the maybes. These maybes are not necessarily drugs or genetic derivatives. Anything a company potentially has to offer is in the pipeline. Immunoassay tests, a new drug delivery system, even the next Pentium computer chip is in the pipeline if it is not yet being sold in stores. An artist working on their latest music album has a project in the pipeline. Hey, even this article was in the pipeline until being scanned by you, the reader. Tara Breton, Health Advances LLC,  Working the Pipeline Databases,  Searcher 11(8) Sept. 2003.

New medicine in development database, PhRMA http://www.phrma.org/newmedicines/

Narrower Terms: hollow pipeline, robust pipelines; Related terms: Drug approvals  NCE, NDA, Phase I, Phase II, Phase III, Phase IV  See also pipelines, therapeutic

drug ontology: A three year project to develop a highly structured drug knowledge base. Unlike existing reference sources, it is intended solely for use by software applications. http://www.cs.man.ac.uk/mig/projects/old/drugontology/index.html

drug prototypes:  Considered to be the first pure compound to have been discovered in any series of chemically or developmentally related therapeutic agents. A few prototypes have not been developed further because this has been unnecessary, commercially unacceptable or else unsuccessful. Some prototypes continue to serve as medicinal compounds in their own right, while others have been rendered obsolete by the analogues derived from them. Dr. Walter Sneader, author of Drug Prototypes and their Exploitation. John Wiley, 1996, Strathclyde Institute for Biomedical Sciences, Glasgow, http://spider.science.strath.ac.uk/PharmSci/showPage.php?deptID=3&u=ceas04&includePage=staffDetails.php   

Related term: analogue based drug discovery

drug repositioning: Involves determining novel uses for existing drugs and rescuing failed compounds. Major benefits of this approach include shorter development cycles, faster drug approval, and the ability to capitalize on the repertoire of drug candidates. Different approaches will be presented for identifying additional indications for compounds, screening against new targets, evaluating patent life, and identifying medical need. Lessons learned will include how to harness creativity to invent new niche markets or diseases. Drug Repositioning  Oct 10-11, 2007 • Philadelphia, PA

drug safety: Drug Safety, Pharmacovigilance & Postmarketing surveillance

drug selection:  Traditionally the movement of compounds along the pipeline has been a fairly linear process.  Because ways of speeding up the process can be enormously economically rewarding, greater attention is being paid to moving compounds along faster, trying to insure that compounds which will eventually fail, fail earlier, and looking at ways of revising the process to perform some evaluations in parallel rather than sequentially. 

drug target, drug targeting: Drug Targets

druggable: Able to be modulated by a small molecule to produce a desired phenotypic change in cell targets.  

Variant spelling is drugable, however Google had about 283 hits (Nov 16, 2001) for druggable (July 18, 2002 = about 445; about 1,030 Aug. 22, 2003), with about 138 for drugable Nov. 16, 2001 (about 248 July 18, 2002; about 548  Aug. 21, 2003).

Related terms: low hanging fruit, pharmaceutically tractable, small molecules, tractable targets  privileged structure; Pharmaceutical biology G proteins, ion channels

drug-like, drug-likeness: Aqueous solubility and permeability data must be provided to chemistry as early as possible to avoid oral absorption problems. The minimum acceptable solubility for a drug depends on its permeability and projected clinical potency. Christopher Lipinski, The Design of Drug- Like Properties, ACD & European User Meeting, Nov. 7- 8,  2001, Obernal, France http://www.acdlabs.com/um/eum2001/lipinski.html 

Google Mar. 5, 2004 = drug-like: about 61,500; Apr 6, 2007 about 523.000 
drug-likeness Mar 5, 2004 about 592, Apr 6, 2007 about 22,200 
druglike Mar 5, 2004 about 976, Apr 6, 2007 about 26,700.

early attrition: Of poor drug candidates is central to the new drug discovery paradigm.  The major trend in lead optimization is the movement toward in silico and high- throughput in vitro approaches. Computational methods can be applied to chemical structures to predict ADMET properties even before the compound is synthesized so that only favorable compounds need be synthesized for screening. Whole cells are also increasingly being used in high- content screening mode to provide selectivity information along with other valuable data concerning the effects of compounds on cell function. Another area of growing impact involves the use of cells equipped with reporter gene constructs for high- throughput analysis of the expression of specific, predetermined genes in response to compound administration. New approaches for predicting toxicity are also examined in this report, particularly the efforts of some groups to develop better animal model systems and to look at ways to introduce these assays earlier in the process. 

early stage compounds: See Alliances licensing

efficacy: Pharmaceutical biology

fail fast approach: Designed to eliminate high risk compounds at an early stage, is designed not to increase the throughput capacity of clinical development, but to free up existing capacity for more successful compounds. The industry will be faced with an increasing number of candidates and targets advanced into development as a result of many factors, including the availability of the human genome sequence. But companies risk actually decreasing their productivity rate if they end up chasing more low quality drug candidates. 

follow–on drug: New entrant to a therapeutic class defined by another drug entity that was the first to receive regulatory approval for marketing. Tufts Center for the Study of  Drug Development, Glossary, 2007  http://csdd.tufts.edu/InfoServices/Glossary.asp 

formulation:  Advancing technologies and increased regulatory scrutiny throughout drug development, have heightened interest in drug formulation and delivery. Applications of methods and technologies to characterize and optimize the physical and chemical properties of drugs. 

Hepatitis C HCV Drug discovery: The existing standard of care for treatment of hepatitis C virus (HCV), pegylated interferon in combination with ribavirin, leaves room for improvement: Only 40–80% of patients are responsive to this regimen (depending on their genotype). Additionally, it requires a lengthy treatment period of up to 48 weeks, and it is plagued by side effects that include neuropsychiatric symptoms, fatigue, anemia, and flu-like symptoms.  Development of HCV protease inhibitors has been challenged by the fact that the active site on the enzyme is very difficult to target— the binding site is extremely shallow. Both HCV protease and polymerase inhibitors face the challenge of drug resistance.  HCV Drug Discovery April 28-29, 2008 • La Jolla, CA  

high throughput: Although the adjective "high throughput" was originally coined in a drug screening context, high throughput strategies to accelerate and automate earlier steps in the drug discovery pipeline have already been introduced. With the introduction of genomics- based drug discovery strategies, the concept of high throughput has extended to areas like gene expression analysis, where microarrays allow the simultaneous expression profiling of thousands of genes in diseased versus normal samples. In the early stages of disease- gene research, when one wishes to identify alterations in gene expression that are associated with a disease state with significant societal impact and potential market value, a microarray- based approach provides significant acceleration over traditional methods to evaluate candidate genes one at a time.   

High Throughput Screening HTS, hit: Assays & screening

hollow pipelines: Drug pipelines lacking promising products, particularly those that seem to be near approval. Compare robust pipelines; Broader term: drug discovery pipeline

immunogenicity: Therapeutic antibodies and proteins in clinical development or on the market to some extent have the potential to be immunogenic. The formation of antibodies to these therapeutic agents may; 1) have no clinical consequence, 2) cause mild to severe adverse effects in patients, and/or 3) effect the efficacy of the agent due to neutralization of drug activity or effects on drug pharmacodynamics and pharmacokinetics. Development of a preclinical and clinical plan to evaluate for the presence of an immune response by assay detection and surveillance of clinical symptoms, suggestive of an immune response, is essential during drug development. Clinical Assessment of the Immunogenicity of Therapeutic Biologics, May 1-2, 2008, Boston, MA

in silico, in silico chemical genomics: In silico & Molecular modeling

in silico screening: See virtual screening Chemoinformatics

India, drug development: Best approaches to outsourcing, in/out-licensing, and risk sharing partnerships Protecting and managing your intellectual property (IP) Local perspectives on what are the true challenges in India Integrating efforts in India with all other worldwide research activities Actionable strategies for launching R&D activities. Drug Development India, Nov 15-16,  2007, Philadelphia PA

infectious diseases: Global sales of anti-infective drugs reached $44.5 billion in 2005 and will likely double over the next 5 years. Antibiotics led the category at $31 billion. ... This report analyzes the factors driving infectious disease therapeutic and diagnostic markets, the key business and technology trends, targets and drugs in development, companies at the forefront of anti-infective R&D, and the commercial opportunities and challenges of anti-infective drugs and vaccines. Past hurdles to pursuing anti-infective drug development―including historically low margins, short therapeutic regimens, manufacturing challenges, and regulatory problems associated with developing drugs for “unvalidated” microbial targets―are no longer discouraging entrants. Insight Pharma Reports, Infectious diseases: R&D Challenges and Market Drivers, 2006

inflammatory diseases pipelines:  This report comprehensively evaluates R&D efforts for six high-profile immune/inflammatory disorders : Rheumatoid Arthritis, Inflammatory Bowel Disease, Psoriasis, Lupus, Multiple Sclerosis, Asthma. The complexity of the immune system provides both opportunity and challenge for those in the pharmaceutical industry trying to manipulate it. There is a seemingly endless list of cytokines, receptors, and enzymes that can be disrupted in patients with autoimmune and inflammatory diseases, and the sheer number of options leaves plenty of chances for large established players and specialized newcomers alike to carve out niches for themselves.  Insight Pharma Reports: Inflammatory Disease Therapeutics: Pipelines and Competitive Dynamics, 2005

kinase therapeutics: The ubiquity of kinases as potential targets means that eventually they will be exploited for virtually every human disease, particularly diabetes, inflammatory disorders, and especially cancer. The success of Novartis’ Gleevec and Roche’s Herceptin has demonstrated that kinase inhibitors for cancer that are effective and well-tolerated can enjoy strong sales. Insight Pharma Reports, Kinase Therapeutics: A wealth of targets sparks a highly active market., 2006

Related terms: Drug Targets kinase inhibitors, protein kinases

LIMS Laboratory Information Management Systems: A basic LIMS is a passive bookkeeping system designed to keep track of laboratory processes. It records the procedures that have been applied to each sample, when a procedure was run, the machine or instrument that was used, and who (e.g., which technician) did the work or was responsible for it. It also records any run-specific parameters of the procedure, and the results if any. In addition, a LIMS typically handles necessary administrative functions, such as inventory management, monitoring of quality measures, resource planning for instruments and personnel, and reporting.  Related terms: robotic systems, robotics, sample prep, Assays & Screening

late stage compounds: See Alliances  licensing

lead, lead generation, lead identification, lead like, lead optimization: Assays & screening

lifestyle drugs: Drugs treating non-life threatening conditions such as  obesity, erectile dysfunction, baldness, aging.  

Pharmaceutical biology ligand

low hanging fruit: The easiest drugs to identify and gain approval for.  The big question these days is how much (if any) "low hanging fruit" is left. 

Related terms: developability, druggable, pharmaceutically tractable, tractable targets

medicinal chemistry: Chemistry & biology 

microdosing:  Pharmacogenomics  Related term: phase zero, phase 0

microplate, microtiter plate, microtitre plate Assays & screening

molecular design: The application of all techniques leading to the discovery of new chemical entities with specific properties required for the intended application. IUPAC Compendium

Related terms: drug design, ligand design, rational drug design.

molecular mimicry: The process in which structural properties of an introduced molecule imitate or simulate molecules of the host. Direct mimicry of a molecule enables a viral protein to bind directly to a normal substrate as a substitute for the homologous normal ligand. Immunologic molecular mimicry generally refers to what can be described as antigenic mimicry and is defined by the properties of antibodies raised against various facets of epitopes on the viral protein. [MeSH from Immunology Letters 28 (2): 91- 99 May 1991]

molecular recognition: The ability of biological macromolecules such as proteins and DNA to recognize selectively and to bind to other species to form larger supramolecular complexes is a key element in the extraordinarily diverse and controlled chemistry exhibited by nature. Chemists today are increasingly interested in mimicking these processes which involve 'molecular recognition' of one molecule by another via formation of specific nonequivalent bonds between them and spontaneous binding together of two to many thousands of molecules into well defined supramolecular systems with new chemical properties. Industrially important applications already include drug design, synthesis of stereo regular polymers, affinity chromatography, crystallization, epitaxial growth and liquid crystal displays. [BD More and M.J. Dustin Molecular Recognition course, University of Strathclyde, Glasgow, Scotland, 2000]   http://www.strath.ac.uk/Departments/Chemistry/courseinfo/4thyear/13944.html

Related terms: molecular mimicry, peptidomimetic, recognition site

molecular targets: Drug Targets

monoclonal antibodies: Drug Targets 

multiplex assays: Assays

NCE New Chemical Entity: Drug approvals

neglected diseases: See sleeper diseases

NME New Molecular Entity: Drug approvals

orphan products: Drug approvals

pathome: It had become increasingly clear with the completion of the human genome project that genotyping alone will have little impact on the medical treatment of chronic diseases. To accomplish this, a better understanding of the pathophysiology of the subsets that underline many of these conditions is required. For example, subdividing hypertensive patients by intermediate phenotypes - traits that are found to be present in some but not all hypertensive subjects - has the potential to substantially increase the power of such genetic approaches. We have termed the collection of these intermediate phenotypes, a Human Hypertension Pathome Project.  [Gordon Harold Williams, Brigham & Women's Hospital, Boston, US "Endocrine Renal and Genetic Factors in Human and Experimental Hypertension, 2001] http://research.bwh.harvard.edu/rdbook/en18.htm

pathway analysis:  Decipher the function of key pathways and address the selection of compounds to obtain  desired physiologic function  Molecular Medicine Marketplace:  Pathway Analysis for Target and Compound Evaluation, Feb. 22-24, 2006, San Francisco, CA

pharmaceutical bioinformatics: Bioinformatics

pharmaceutical process chemistry: Chemistry & biology

pharmaceutical forecasting: The main goal in Phase I and II drug development is to find dose ranges in humans that induce minimal or no obvious toxicity and that result in some detectable level of effectiveness for the desired indication. Insight Pharma Reports, Bayesian Forecasting of Phase III Outcomes: The Next Wave in Predictive Tools, June 2007  

pharmaceutical industry: Business of biopharmaceuticals

pharmaceutical profiling: The pharmaceutical properties of drug candidates determine how much of the drug safely reaches the therapeutic target. Drug candidates often fail in discovery and development due to inadequate properties, resulting in lost opportunities and resources for developing new drugs. Pharmaceutical profiling assays have been developed and implemented to measure the properties of large numbers of drug candidates starting at the earliest stages of discovery. This information is used for informed decisions in drug candidate selection and synthetic optimization. A holistic process of parallel activity and property optimization has emerged in drug discovery. EH Kerns, L. Di, Multivariate pharmaceutical profiling for drug discovery, Current Topics in Medicinal Chemistry 2 (1): 87-98, Jan. 2002

pharmaceutically tractable: Related terms: developability, druggable, low hanging fruit, tractable targets

pharmacodelivery: Site-directed pharmacodelivery is a desirable but elusive goal. Endothelium and epithelium create formidable barriers to endogenous molecules as well as targeted therapies in vivo. Deidre P. MacIntosh et. al, Targeting endothelium and its dynamic caveolae for tissue-specific transcytosis in vivo: A pathway to overcome cell barriers to drug and gene delivery, PNAS 99 (4): 1996-2001, Feb. 19, 2002 http://www.pnas.org/cgi/content/full/99/4/1996 

pharmacoinformatics: PHARMINFO (Pharmacoinformatics Network) is an interdisciplinary moderated discussion forum dedicated to various aspects of implementation and use of modern information technologies in pharmacy practice, pharmacy education, drug design and development, and related fields. [Iosif Vaisman, "E-drug: Pharmacoinformatics" 12 Nov. 1998] 

Google May 9, 2002 = about 248 websites.  May 27, 2003 about 367; about 33,900 Nov 10, 2006

Related term: pharmainformatics

pharmacophore: Pharmaceutical biology

pharmainformatics: The multidisciplinary informatics needs of the pharmaceutical industry (HTS High Throughput Screening) data, combinatorial chemistry, ADME informatics, cheminformatics, toxicology, etc. information access and communication between various departments like the development and discovery teams. [CCL [Computational Chemistry List] call for papers, Spring ACS [American Chemical Society] meeting in San Diego (April 1-5, 2001) Sponsored by the Biotechnology Secretariat (BTEC) Co-sponsored by Chemical Information Division (CINF)]   http://www.quimica.urv.es/~bo/llistes/CCL/100/10/msg00081.html

Google May 9, 2002 = about  106 websites. May 27, 2003 about 208; about 952 Nov 10, 2006

Related term: pharmacoinformatics

pharmacovigilance: Drug Safety, Pharmacovigilance & Postmarketing surveillance

pharming: Genetic manipulation & disruption

phase zero, phase 0: Drug approvals  Related term: microdosing

pipeline problem:  Is it better to fund single or multiple approaches to disease opportunities, and , if multiple, how many? Insight Pharma Reports, Backup Compound Strategies: Best Practices for Reducing Phase II Risk, 2007

Innovation or Stagnation: Challenge and Opportunity on the critical path to new medical products, FDA, March 2004 http://www.fda.gov/cber/gdlns/pharmdtasub.pdf 

pipelines, therapeutic: Insight Pharma Reports Series  http://www.insightpharmareports.com/Reports/TherapeuticPipelinesAndDiseaseMarkets.aspx 

See also drug discovery pipeline

post marketing surveillance: Drug Safety, Pharmacovigilance & Postmarketing surveillance 

preclinical development: The area of preclinical development is critical to ensuring the safety of all drugs entering clinical trials and ultimately the marketplace. Molecular approaches to assess drug candidate toxicity and human metabolism will help to better predict safety and efficacy early in the development process. Developing more specific assays for genetic toxicology will be a key contribution to this effort. The use of modeling could shed light on the relationship between PK/PD and toxicity, and help to translate results to human in vivo response. Improvements and innovations in preclinical in vitro assays and animal models will lead to greater compound yield and lower costs. Preclinical development: How can we improve prediction of clinical safety? Molecular Medicine, March 2008, San Francisco CA 

Google = about 507,000 preclinical development July 31, 2007
Google = about 41,400 preclinical drug development July 31, 2007

Wikipedia http://en.wikipedia.org/wiki/Pre-clinical_development 

Related terms: Drug safety & pharmacovigilance

preclinical drug evaluations: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.  MeSH, 1974

preclinical investigations: Laboratory and animal studies designed to test the mechanisms, safety, and efficacy of an intervention prior to its applications to humans [IRB]

preclinical research: During preclinical drug development, a sponsor evaluates the drug's toxic and pharmacologic effects through in vitro and in vivo laboratory animal testing. Genotoxicity screening is performed, as well as investigations on drug absorption and metabolism, the toxicity of the drug's metabolites, and the speed with which the drug and its metabolites are excreted from the body. At the preclinical stage, the FDA will generally ask, at a minimum, that sponsors: (1) develop a pharmacological profile of the drug; (2) determine the acute toxicity of the drug in at least two species of animals, and (3) conduct short-term toxicity studies ranging from 2 weeks to 3 months, depending on the proposed duration of use of the substance in the proposed clinical studies.  FDA, CDER, Drug Development and Review Definitions, 2001 http://www.fda.gov/cder/handbook/preclin.htm 

preclinical studies: Studies that test a drug on animals and other nonhuman test systems. They must comply with FDA's good laboratory practices. Data about a drug's activities and effects in animals help establish boundaries for safe use of the drug in subsequent human testing (clinical studies). Also, because animals have a much shorter lifespan than humans, valuable information can be gained about a drug's possible toxic effects over an animal's life cycle and on offspring. Drug Review Glossary, FDA Consumer Magazine, 25 definitions http://www.fda.gov/fdac/special/newdrug/bengloss.html 

preclinical testing: Compounds are tested on cell lines (human and animal) for effectiveness. Also, the compounds are tested in live animals for toxicity and to ensure that they maintain their pharmacological properties. 

protein delivery: There is enormous potential for innovative drug delivery approaches to expand the biologics pipeline, and improve properties of biologic drugs. Engineering approaches can enhance pharmacokinetic properties to make possible non- traditional delivery routes for proteins, such as transdermal, oral, inhalation. Increasing the success rate of novel therapeutic entities involves employing drug delivery solutions earlier in discovery.  Engineering Proteins for Delivery April 30- May 1, 2008, Boston MA

It is a safe bet that if a therapeutic protein is bringing in big money and its patent is nearing expiration, someone somewhere with a clever technology is planning a market invasion based on improving how the protein is delivered. Insight Pharma Reports Delivery Technologies for Protein Therapeutics: Assessment and Outlook  2007

protein therapeutics: The demand for protein-based therapeutics grows by 50% each year, yet the time-consuming and often unpredictable nature of working with peptide and protein-based therapeutics is hampered by the tremendous cost of developing a product – up to $3 billion.  PepTalk: Peptide and Protein-based Therapeutics January 7 - 9, 2008, San Diego CA 

protein therapeutics delivery: See protein delivery

prototypes: First in class compounds usually directed at a specific molecular target. (Note that we have adapted the term for use in a broader sense to replace the term lead compound, which arguably loses some of its meaning after the4 lead optimization process.)  Insight Pharma Reports, Backup Compound Strategies: Best Practices for Reducing Phase II Risk, 2007

rational drug design: The input of biocomputing in drug discovery is twofold: firstly the computer may help to optimise the pharmacological profile of existing drugs by guiding the synthesis of new and "better" compounds. Secondly, as more and more structural information on possible protein targets and their biochemical role in the cell becomes available, completely new therapeutic concepts can be developed. The computer helps in both steps: to find out about possible biological functions of a protein by comparing its amino acid sequence to databases of proteins with known function, and to understand the molecular workings of a given protein structure. Understanding the biological or biochemical mechanism of a disease then often suggests the types of molecules needed for new drugs.  [Wolfram Altenhogen "Biocomputing and drug design, 1996] http://www.techfak.uni-bielefeld.de/bcd/ForAll/Introd/drugdesign.html

Related terms: structure based design; Combinatorial Libraries & synthesis: rational library design; In silico & molecular modeling especially computational quantum chemistry

recombinant antibodies: Drug targets

repositioning: Pharmaceutical process R&D professionals such as chemists, engineers and analysts are constantly being tasked with a difficult challenge: How to improving process efficiency, safety and yield while simultaneously reducing API cost and greatly increasing the speed of development? To solve these problems requires creativity, the right tools, and an up-to-date skill set of best practices and knowledge.  Drug repositioning, Oct. 10- 11, 2007, Philadelphia PA

repurposing: See repositioning

RNAi target validation: Drug Targets

RNAi therapeutics: RNA

robot: The word 'robot' was coined by the Czech playwright Karel Capek (pronounced "chop'ek") from the Czech word for forced labor or serf. ...The use of the word Robot was introduced into his play R.U.R. (Rossum's Universal Robots) which opened in Prague in January 1921. The play was an enormous success and productions soon opened throughout Europe and the US. R.U.R's theme, in part, was the dehumanization of man in a technological civilization. You may find it surprising that the robots were not mechanical in nature but were created through chemical means. [Comp-AI Robotics FAQ] 

robotic system: Automated device where materials are transferred by the physical movement of a delivery device relative to the ultimate receptacle, or vice versa. See also fluidic system. [IUPAC Combinatorial Chemistry]

robotics:  "A reprogrammable, multifunctional manipulator designed to move material, parts, tools, or specialized devices through various programmed motions for the performance of a variety of tasks" Robot Institute of America, 1979  Obviously, this was a committee-written definition. It's rather dry and uninspiring. Better ones for 'robotics' might include: Force through intelligence. Where AI meet the real world. ...refers to the study and use of robots. The term was coined and first used by the Russian- born American scientist and writer Isaac Asimov (born Jan. 2, 1920, died Apr. 6, 1992). [Comp- AI Robotics FAQ] http://www.frc.ri.cmu.edu/robotics-faq/1.html#1.1

robust: Algorithms & data management

robust pipelines: Best identified in retrospect.  Predicting which drugs will be most profitable is difficult (if not impossible).  Drug pipelines can be filled with promising products, but successful use in humans is the ultimate validation. Compare hollow pipelines; Broader term: drug discovery pipeline

scalable: Capable of being expanded for high- throughput. Analogous to recipes optimized for large groups, rather than standard recipes being quadrupled or more, with less than ideal results. Also spelled scaleable.

screen, screening: Assays & screening

sleeper diseases: Sleeper diseases comprise a broad spectrum of increasingly recognized conditions with various degrees of neuropsychiatric involvement. Many of these conditions are now clearly defined, earning them increasing acceptance as real disorders that can and should be addressed by pharmacotherapy. Covers autism; compulsions, phobias, panic attacks; chronic fatigue system, fibromyalgia, eating disorders, restless leg syndrome.   Insight Pharma Reports, Sleeper diseases: Forecast and Assessment of Neglected Disease Market Opportunity, 2006 

small molecule therapeutics, small molecules: Low molecular-weight drugs. Compared to larger molecular weight pharmaceuticals such as proteins, peptides, and carbohydrates, small molecules can more easily penetrate cell membranes and the blood brain barrier. Can be delivered orally or intravenously. These molecules tend to incur lower process development and manufacturing costs.  

Preferred for drugs as they are orally available (unlike proteins which must be administered by injection or topically). Size of small molecules is generally under 1000 Daltons, but many estimates seem to range between 300 to 700 Daltons.

Related terms: druggable, low hanging fruit, pharmaceutically tractable

space: Combinatorial libraries & synthesis  Narrower terms: chemical space, diversity space, property space; spatially addressable

SAR Structure Activity Relationship: Cheminformatics

systems biology: Genetic manipulation & disruption

target, target discovery, target glut,  target evaluation,  target identification, target prioritization, target qualification:  , target screening, target validation, target validation technologies: Drug Targets

translational research: Research

Ultra High Throughput screening uHTS: Assays & screening

vaccine: An agent containing antigens produced from killed, attenuated or live pathogenic microorganisms, synthetic peptides or by recombinant organisms, used for stimulating the immune system of the recipient to produce specific antibodies providing active immunity and/or passive immunity in the progeny. [IUPAC Compendium] 

Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. MeSH

Vaccine Research publications, National Institute of Allergies & Infectious Diseases, NIH, US http://www.niaid.nih.gov/publications/vaccine.htm

Narrower terms: allogeneic polyvalent vaccines,  allogenic vaccines, autologous vaccines,  DNA vaccine; 
Related terms: reverse vaccinology;  -Omes & -omics: vaccinome, vaccinomics

vaccines - novel: The topic of vaccines has entered the forefront of the public’s thoughts and emotions as new diseases threaten the global population. Large numbers of vaccines are needed, yet burdensome production methods require facilities that do not exist. Innovations are required to bring vaccines into a new age of design, production, and delivery. Developing novel vaccines involves myriad challenges as manufacturers hustle to meet growing demands. Novel Vaccines: Bridging Research, Development, and Production, August 22-24, 2007, Cambridge MA

virtual medicinal product: A SNOMED concept http://www.snomed.org/snomedct/documents/snomed_ct_user_guide.pdf 

virtual screening: In silico & molecular modeling

World Pharmaceutical Congress May 12-14, 2008, Philadelphia, PA    Novel approaches to Optimization    Animal models for drug discovery and pain   Cell Based Assays for HTS     Cardiotoxicity  and Drug Safety

xenobiotic: Drug safety & pharmacovigilance

Bibliography
FDA, CDER, From Test Tube to Patient, Improving Health through Human Drugs, 1999 http://www.fda.gov/cder/about/whatwedo/testtube-full.pdf
IUPAC International Union of Pure and Applied Chemistry, Nomenclature in laboratory robotics and automation, 1994 http://www.iupac.org/publications/pac/1994/pdf/6603x0609.pdf
Nature Drug Discovery gateway, Nature Publishing Group http://www.nature.com/cgi-taf/gateway.taf?g=5&file=/drugdisc/res_high/articles/nrd922.html
Nature, Rethinking Drug Discovery, 19 March 2004 http://www.sciencemag.org/sciext/drugdisc/ 

Alpha glossary index

How to look for other unfamiliar  terms

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