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Drug discovery & drug development glossary & taxonomy
Evolving Terminologies for Emerging Technologies
Comments? Suggestions? Revisions? Mary Chitty mchitty@healthtech.com
Last revised February 04, 2014
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Chemistry term index   Drug discovery term index   Informatics term index   Technologies term index    Biology term index  Finding guide to terms in these glossaries  Glossaries & Taxonomies Site Map   Therapeutic areas: covers cancer & oncology, cardiovascular, CNS & neurology, Immunology, Infectious diseases, and Inflammation  Biologics is a subset of this glossary  Related glossaries include  Clinical trials    Drug Safety, Pharmacovigilance & Post Marketing Surveillance    Drug targets     Pharmacogenomics  Regulatory  Business  Business of biopharmaceuticals   Clinical trials, drug, device & diagnostics approvals   Finance & Pharmacoeconomics    Pharmaceutical Intellectual property    Chemistry  Assays & screening   Chemistry Medicinal & Pharmaceutical  Combinatorial libraries & synthesis
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Biology  Pharmaceutical biology    

Genomics and proteomics can be used in compound evaluation, by providing molecular details about the effect of a compound on the body. This approach may highlight mechanisms of action or toxicity, both of which can be critical for further compound optimization. 

Accelerating Medicines Partnership: a bold new venture between the NIH, 10 biopharmaceutical companies and several non-profit organizations to transform the current model for developing new diagnostics and treatments by jointly identifying and validating promising biological targets of disease. The ultimate goal is to increase the number of new diagnostics and therapies for patients and reduce the time and cost of developing them. http://www.nih.gov/science/amp/index.htm

ADAPT Accelerating Development and Advancing Personalized therapies September 19-21, 2012 • Washington, DC Program | Register | Download Brochure

agonist(s): An endogenous substance or a drug that can interact with a receptor and initiate a physiological or a pharmacological response characteristic of that receptor (contraction, relaxation, secretion, enzyme activation, etc.) [IUPAC Medicinal Chemistry] Contrast with antagonist(s).

agonist activity: The potency of activating drugs varies tremendously in different cells making measures of absolute potency for predicting therapeutic of very limited value. This session discusses how dose-response curves can be reduced to cell-type independent parameters describing the molecular properties of affinity and efficacy through application of the Black/Leff operational model of agonism. Biased agonism also is discussed in terms of the assays and parameters that can be used to determine functionally selective effect.  Quantifying Receptor Activation and Agonism: Why Measuring Only Potency Falls Short Dec 14 2011 Global Web Symposium

analog: A drug whose structure is related to that of another drug but whose chemical and biological properties may be quite different. [IUPAC Medicinal Chemistry] Compare congener.

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 terms: drug prototypes,  Regulatory Affairs: follow ons,  me too drugs

animal disease models: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases. MeSH 1970

animal models: Although animal models based on mammalian species have been long employed, more recently the pharmaceutical/biotechnology industry has also adopted several invertebrate and lower vertebrate animal models. The aim of using animal models to develop novel therapeutic strategies is to achieve knowledge of pathways and targets that leads to new paradigms for drug discovery and development. Insight Pharma Reports Animal Models for Therapeutic Insights, 2010     See also Model organisms

antagonist: A drug or a compound that opposes the physiological effects of another. At the receptor level, it is a chemical entity that opposes the receptor- associated responses normally induced by another bioactive agent. [IUPAC Medicinal Chemistry] Compare agonistRelated term: selective modulators

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

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

BioIT World Weekly Update: Drug discovery & development preclinical http://www.bio-itworldweekly.com/category/4/drug-discovery-development-preclinical/ 

biological availability: The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. MeSH 1979  Also known as bioavailability.

blockbuster drugs: Business of biopharmaceuticals

breakthrough therapies: The Food and Drug Administration Safety and Innovation Act (FDASIA) includes a provision that allows sponsors to request that their drug be designated as a Breakthrough Therapy.  FDA is in the process of developing guidance related to this designation. Until guidance is developed, requests for Breakthrough Therapy designation should follow the criteria outlined below. …   A request for Breakthrough Therapy designation should be submitted concurrently with, or as an amendment to an Investigational New Drug Application (IND) with a cover letter, a completed form 1571, and the following information: … Breakthrough Therapy designation for the indication being studied, including: Evidence that the drug is intended, alone or in combination with 1 or more other drugs, to treat a serious or life-threatening disease or condition, Preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.  US FDA, Regulatory Information, Fact Sheet: Breakthrough Therapies 2012 http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm

chemical biology, chemical genetics, chemical genomics, chemical ligand studies, chemogenomics: Chemistry  
clinical development, clinical trials: clinical forecasting: Clinical trials

combination drug/diagnostic products: As examples of drug/diagnostic combinations succeed in the market, interest in this field continues to grow and offers promising opportunities for novel products.  This report provides a comprehensive look at all available combination therapeutic and diagnostic products from regulatory required co-marketed products to label recommended combinations and identifies factors leading to market success. Insight Pharma Reports, Combination Drug Diagnostics: Fueling Growth of Personalized Medicine    2010

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/ 
more at Regulatory Affairs

combination therapies: 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

co-development drugs & diagnostics, companion diagnostics: Molecular diagnostics

Critical path:  The Critical Path Initiative (CPI) is FDA's national strategy to drive innovation in the scientific processes through which medical products are developed, evaluated, and manufactured. The Initiative was launched in March 2004, with the release of FDA's landmark report Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products1. The publication diagnosed the reasons for the widening gap between scientific discoveries that have unlocked the potential to prevent and cure some of today's biggest killers, such as diabetes, cancer, and Alzheimer's, and their translation into innovative medical treatments.  http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/ucm076689.htm 

On March 16 [2004], FDA released a report addressing the recent slowdown in innovative medical therapies submitted to the FDA for approval, "Innovation/ Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products." That report describes the urgent need to modernize the medical product development process -- the Critical Path -- to make product development more predictable and less costly. FDA, The critical path to new medical products,  http://www.fda.gov/oc/initiatives/criticalpath/    

De-Risking Drug Discovery  February 21-23, 2012 • San Francisco, CA Program | Register | Download Brochure

developability:
This article describes the role and responsibilities of the Developability Assessment Group (DAG), a pharmaceutical Research and Development (R&D) subgroup, which supports drug discovery and development scientists with screening, developability assessment, and selection of new molecular entities (NMEs) for clinical studies. A strong collaboration between discovery group and DAG is essential for selecting the right NMEs for late-stage development, and consequently decreasing the NME attrition rate in late-stage development as well as in bringing down the associated cost and timelines. The investigations performed by DAG for evaluating research leads as well as the significance of these investigations in the developability assessment, the value of cutting edge tools and technologies, and the usefulness of the data in the decision making process are discussed in this review. Developability assessment of NMEs often includes physicochemical and biopharmaceutical characterization, development of suitable formulations for pharmacokinetic (PK), efficacy, and toxicity studies, selection of suitable physical form (salt, polymorph, etc.), and formulation development for phase I clinical studies. Overall DAG activities not only contribute to streamlining efficacy-toxicology evaluation, but also in building developability screens, which allow pharmacologically effective, minimally toxic, and developable candidates to reach the clinic and eventually to the market. J Pharm Sci. 2009 Jun;98(6):1962-79. doi: 10.1002/jps.21592. Developability assessment in pharmaceutical industry: An integrated group approach for selecting developable candidates.  Saxena VPanicucci RJoshi YGarad S. http://www.ncbi.nlm.nih.gov/pubmed/18855914

disease targets: Drug Targets
drug: Regulatory Affairs

drug development: Process of optimizing compounds following drug  discovery. 
Wikipedia http://en.wikipedia.org/wiki/Drug_development 
Drug Development: Evolving Challenges and Opportunities
, 2008 Webcast Joshua Boger, Ph.D., President & CEO, Vertex Pharmaceuticals, http://www.bio-itworld.com/lsw/jboger.aspx 
Related terms: attrition, hit to lead, lead optimization, lead validation

drug discovery:   Wikipedia http://en.wikipedia.org/wiki/Drug_discovery   Related terms: drug development,  drug discovery chemistry    target validation

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.  Narrower Terms: hollow pipeline, robust pipelines; Related terms: Regulatory Affairs  NCE, NDA, Phase I, Phase II, Phase III, Phase IV  See also pipelines, therapeutic
Medicines in the pipeline,
PhRMA http://phrma.org/pipeline

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, Drug Prototypes and their Exploitation. John Wiley, 1996, Related term: analogue based drug discovery

drug repositioning: Drug repositioning has become a matter of intense interest during the past few years. It is an approach to drug development that calls for reinvestigation of candidates that did not succeed in advanced clinical trials (for reasons other than safety) for potential use in other therapeutic indications. Insight Pharma Reports Drug Repositioning: Extracting Added Value from Prior R&D Investments 2010  Also known as drug repurposing

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. 

druggability: the likelihood of being able to modulate a target with a small-molecule drug — is crucial in determining whether a drug discovery project progresses from 'hit' to 'lead'. With only 10% of the human genome representing druggable targets, and only half of those being relevant to disease, it is important to be able to predict how druggable a novel target is in early drug discovery. Nature Reviews Drug Discovery 6, 187 (March 2007) | doi:10.1038/nrd2275 Determining druggability Joanna Owens  http://www.nature.com/nrd/journal/v6/n3/full/nrd2275.html
Wikipedia
http://en.wikipedia.org/wiki/Druggability

druggable: the likelihood of being able to modulate a target with a small-molecule drug — is crucial in determining whether a drug discovery project progresses from 'hit' to 'lead'. With only 10% of the human genome representing druggable targets, and only half of those being relevant to disease, it is important to be able to predict how druggable a novel target is in early drug discovery. Nature Reviews Drug Discovery 6, 187 (March 2007) | doi:10.1038/nrd2275 Determining druggability Joanna Owens  http://www.nature.com/nrd/journal/v6/n3/full/nrd2275.html

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

Variant spelling is drugable, however on Feb 22 2011 Google has about 67,900 hits for druggable Feb 22 2011 and about 20,500 for drugable 
Earlier Google results Related terms: low hanging fruit, pharmaceutically tractable, small molecules, tractable targets  privileged structure; Pharmaceutical biology G proteins, ion channels

drug-like, drug-likeness: There are currently about 10000 drug-like compounds. These are sparsely, rather than uniformly, distributed through chemistry space. True diversity does not exist in experimental combinatorial chemistry screening libraries. Absorption, distribution, metabolism, and excretion (ADME) and chemical reactivity-related toxicity is low, while biological receptor activity is higher dimensional in chemistry space, and this is partly explainable by evolutionary pressures on ADME to deal with endobiotics and exobiotics. ADME is hard to predict for large data sets because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates. Drug-like properties and the causes of poor solubility and poor permeability. Lipinski CA. J Pharmacol Toxicol Methods. 2000 Jul-Aug;44(1):235-49

Wikipedia http://en.wikipedia.org/wiki/Druglikeness 

early stage compounds: See Alliances licensing

efficacy:
Describes the relative intensity with which agonists vary in the response they produce even when they occupy the same number of receptors and with the same affinity. Efficacy is not synonymous to intrinsic activity. The property that enables drugs to produce responses. 

It is convenient to differentiate the properties of drugs into two groups, those which cause them to associate with the receptors (affinity) and those that produce stimulus (Efficacy). This term is often used to characterize the level of maximal responses induced by agonists. In fact, not all agonists of a receptor are capable of inducing identical levels of maximal responses. Maximal response depends on the efficiency of receptor coupling, i.e., from the cascade of events, which, from the binding of the drug to the receptor, leads to the observed biological effect. [IUPAC Medicinal Chemistry] See also definition in  IUPAC Provisional glossary Biomolecular Screening  Is this related to efficacy as required by the FDA for regulatory approval?

epigenetic drug & diagnostic pipelines: Genetic variations

ethical drugs: The old term ethical drugs signified drugs advertised only to doctors. The expression refers to the original 1847 code of ethics of the AMA, which deemed advertising directly to the public to be unethical. Over time, the term came to mean legal drugs. FDAReview.org, Independent Institute, 2003 http://www.fdareview.org/glossary.shtml#ethical 
Related term: prescription drugs
 

fail fast: Several high-quality analyses comparing the track record of smaller biotechnology companies with established pharmaceutical companies have concluded that company size is not an indicator of success in terms of R&D productivity … the strongest single correlator with success (odds ratio 3.9) was having a high termination rate in preclinical/Phase I stages. This indicates that companies have an early idea of which assets are likely to succeed, and that the compa,nies most willing to face the hard decisions about which assets to terminate do better than companies that let assets linger. Does size matter in R&D productivity? If not, what does? Michael Ringel, Peter Tollman, Greg Hersch and Ulrik Schulze Nature Reviews Drug Discovery 12:901-902, Dec 2013  http://www.nature.com/nrd/journal/v12/n12/pdf/nrd4164.pdf

Designed to eliminate high risk compounds at an early stage to free up existing capacity for more successful compounds. The industry is faced with an increasing number of unvalidated or poorly validated candidates and targets. Companies risk decreasing their productivity rate if they end up chasing more low quality drug candidates. There isn't enough matter in the universe to make all possible compounds.  

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 

genomic drugs:  More than 100,000 people die each year from adverse responses to medications that are beneficial to others. Another 2.2 million experience serious reactions, while others fail to respond at all. ...  Genomic data and technologies also are expected to make drug development faster, cheaper, and more effective. Most drugs today are based on about 500 molecular targets; genomic knowledge of the genes involved in diseases, disease pathways, and drug- response sites will lead to the discovery of thousands of new targets. New drugs, aimed at specific sites in the body and at particular biochemical events leading to disease, probably will cause fewer side effects than many current medicines. Ideally, the new genomic drugs could be given earlier in the disease process. As knowledge becomes available to select patients most likely to benefit from a potential drug, pharmacogenomics will speed the design of clinical trials to bring the drugs to market sooner.  [Medicine and the New Genetics: Genomic and its impact on Medicine and Society, A 2001 primer, Oak Ridge National Lab, US] http://www.ornl.gov/hgmis/publicat/primer2001/6.html   Narrower terms: Gleevec, Herceptin

GLP Good Laboratory Practice: Regulatory

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.   

in silico, in silico chemical genomics: Drug discovery informatics

inhibitors: A substance that diminishes the rate of a chemical reaction. The process is called inhibition. Inhibitors are sometimes called negative catalysts but since the action of an inhibitor is fundamentally different from that of a catalyst this terminology is discouraged. In contrast to a catalyst, an inhibitor may be consumed in the course of a reaction. ... See also effector. [IUPAC Compendium]  Narrower term: promiscuous inhibitors

intrinsic activity:  The maximal stimulatory response induced by a compound in relation to that of a given reference compound (See also partial agonist) This term has evolved with common usage. It was introduced by Ariëns as a proportionality factor between tissue response and receptor occupancy. The numerical value of intrinsic activity (alpha) could range from unity (for full agonists, i.e., agonist inducing the tissue maximal response) to zero (for antagonists), the fractional values within this range denoting partial agonists. Ariëns' original definition equates the molecular nature of alpha to maximal response only when response is a linear function of receptor occupancy. This function has been verified. Thus, intrinsic activity, which is a drug and tissue parameter, cannot be used as a characteristic drug parameter for classification of drugs or drug receptors. For this purpose, a proportionality factor derived by null methods, namely, relative efficacy, should be used. Finally, "intrinsic activity" should not be used instead of "intrinsic efficacy". A "partial agonist" should be termed "agonist with intermediate intrinsic efficacy" in a given tissue.  [IUPAC Medicinal Chemistry]

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

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

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, drug-likeness, pharmaceutically tractable, tractable targets

mechanism of action: Pharmacogenomics

microdosing: The concept of microdosing calls for the administration of an investigational compound to healthy human volunteers in doses at least two orders of magnitude lower than those that, based on animal studies, would have a pharmacological effect in humans. There is also a fixed ceiling dose (100 μg) that must not be exceeded. Insight Pharma Reports, Microdosing in Translational Medicine: Pros and Cons,  2006    Related term: phase zero, phase 0

molecular therapeutics: Biologics
NCE New Chemical Entity: Regulatory Affairs
orphan products: Regulatory Affairs
outsourcing: Business of biotechnology & pharmaceuticals
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: Our drug discovery process begins with our Genome5000 program, in which we are using our gene knockout technology in mice to discover the physiological functions of 5,000 human genes over five years. There are 30,000 genes in the human genome. Of these, roughly 8,700 would fit into pharmaceutically tractable gene families, meaning that they would be amenable to small molecule drug discovery. These could also be antibody targets or secreted proteins themselves. Of those estimated 8,700 tractable genes, about 5,000 have unknown function. Using Knockout Modeling to Uncover the Druggable Genome: An Interview with Brian Zambrowicz of Lexicon Genetics  Molecular Med Monthly July 2004   http://www.chidb.com/newsarticles/issue44_1.asp  Related terms: developability, druggable, low hanging fruit, tractable targets

Phase zero, Phase O: Phase Zero is a novel pre-clinical testing service that combines a range of integrated technologies and involves the introduction of human tissue at the earliest stages of drug development. It allows target identification and validation as well as testing the viability of drug leads and candidates in human tissue before entering the clinic. This enables rationalization of the drug development process and improves the outcome at several points along the developmental path.  Pharmagene signs new Phase Zero agreement with Taisho, Friday, March 09, 2001  http://www.pharmabiz.com/article/detnews.asp?articleid=6449&sectionid=14   Related terms: microdosing   Biomarkers type 0 biomarker  

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 product
s, 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

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. 
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, 2010 http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/ucm176522.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. 

proof of concept drug development: Drug discovery informatics

property based drug design: One of the most challenging aspects of drug discovery remaining is the identification of new molecular entities (NMEs) with the desirable physicochemical properties and absorption, distribution, metabolism, and excretion (ADME) profiles that can be formulated into safe and efficacious drug products. Property-Based Drug Design  May 22-23, 2014 • Boston, MA Program | Register | 


prototypes: Drug & disease targets

research tools:  We use the term "research tool" in its broadest sense to embrace the full range of resources that scientists use in the laboratory, while recognizing that from other perspectives the same resources may be viewed as "end products." For our purposes, the term may thus include cell lines, monoclonal antibodies, reagents, animal models, growth factors, combinatorial chemistry libraries, drugs and drug targets, clones and cloning tools (such as PCR), methods, laboratory equipment and machines, databases and computer software. .. NIH Working Group on Research Tools, June 4, 1998  http://www.nih.gov/news/researchtools/ 

RNAi therapeutics: Following an overview of the discovery and evolution of the RNAi and miRNA field, RNAi Therapeutics: Second-Generation Candidates Build Momentum turns to the science behind therapeutic RNAi and miRNA, technologies for design of therapeutic oligonucleotides that work via an RNAi or miRNA-modulating mechanism, technologies for design of delivery vehicles, and leading companies in the therapeutic RNAi/miRNA industry sector as well as the role of large pharmaceutical companies in the sector. Insight Pharma Reports RNAi Therapeutics 2010

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.

small molecules: Small molecules, often with molecular weights of 500 or below, are extremely important for researchers to explore function at the molecular, cellular, and in vivo level. Such molecules have also proven valuable for treating diseases, and most medicines marketed today are from this class. A key challenge is to identify small molecules effective at modulating a given biological process or disease state.  NIH Common Fund, Molecular Libraries https://commonfund.nih.gov/Molecularlibraries/overview.aspx

Size of small molecules is generally under 1000 Daltons, but many estimates seem to range between 300 to 700 Daltons.

small molecule therapeutics, : 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). . Related terms: druggable, low hanging fruit, pharmaceutically tractable; small molecule libraries

therapeutic engineering: The combined application of the principles of mathematics, engineering, physics, chemistry, and biology to better understand human pharmacology, physiology, toxicology, and pathophysiology with a vision for development of better, more individualized, outcomes- focused, therapeutic treatments. C. Anthony Hunt Lab, Biosystems at Univ. of California, San Francisco, http://biosystems.ucsf.edu/ 

Translational Medicine in Drug Development DVD June 29, 2010 • This first of six seminars will provide an overview of translational medicine activities during the preclinical phase of drug development with several in-depth examples to illustrate specific important concepts.  This seminar will also introduce the entire series where future seminars will focus on target validation, selection and qualification of translational biomarkers, how to use translational science for setting effective decision criteria and detailed case studies in Oncology and Neuroscience.

World Pharma Congress May 21-23, 2014 • Boston, MA Program | Register | Download Brochure

 
World Pharmaceutical Congress

Bibliography
FDA, CDER, From Test Tube to Patient, Improving Health through Human Drugs, 1999 http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/UCM154807.pdf 
Health Commons, Therapy Development in a Networked World, 2008 http://sciencecommons.org/wp-content/uploads/health-commons-whitepaper-launch.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
IUPAC Provisional glossary Biomolecular Screening  2008
MeSH Medical Subject Headings, PubMed http://www.ncbi.nlm.nih.gov/mesh 
Nature Drug Discovery gateway, Nature Publishing Group http://www.nature.com/drugdisc/index.html
Nature, Rethinking Drug Discovery, 19 March 2004 http://www.sciencemag.org/sciext/drugdisc/ 

Drug discovery & development Conferences http://www.chicorporate.com/Conferences/Search.aspx?k=&r=&s=DDV
Accelerating Development & Advancing Personalized Therapy ADAPT http://www.adaptcongress.com/
Discovery on Target http://www.healthtech.com/DOT/
Molecular Medicine Tri Conference http://www.triconference.com/
World Pharmaceutical Congress WPC http://www.worldpharmacongress.com/

Drug discovery & development CDs, DVDs http://www.chicorporate.com/Conferences/CompactDiscs.aspx?s=DDV
Drug discovery & development Short courses http://www.healthtech.com/Conferences_Upcoming_ShortCourses.aspx?s=DDV

Insight Pharma Reports Drug discovery & Development series http://www.insightpharmareports.com/Drug-Discovery-Reports/

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

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