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Drug discovery & drug development glossary & taxonomy
Evolving Terminologies for Emerging Technologies
Comments? Suggestions? Revisions? |
Mary Chitty MSLS
Last revised September 12, 2019

Drug development  includes drug formulation/drug delivery drug repurposing, ADME, biopharmaceutics/, pharmacokinetics, pharmacology.

Biologics is a subset of this glossary 
Therapeutic areas: covers cancer & oncology, cardiovascular, CNS & neurology, Immunology, Infectious diseases, and Inflammation 
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
Informatics  Bioinformatics   Chemoinformatics  Clinical informatics  
Drug discovery informatics    Technologies      Microarrays   Sequencing   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: Accelerating Medicines Partnership (AMP) is a public-private partnership between the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), 12 biopharmaceutical and life science companies and 13 non-profit organizations to transform the current model for developing new diagnostics and treatments by jointly identifying and validating promising biological targets for therapeutics. The ultimate goal is to increase the number of new diagnostics and therapies for patients and reduce the time and cost of developing them.

analogue based drug discovery:  The book Analogue-based Drug Discovery, published by Wiley-VCH in 2006, provided the first authoritative overview of past and current strategies for successful drug development by molecular modification of known leads was. This unique resource spanned the important drug classes in most major therapeutic fields. A second edition* was released this month [2010] that has a broader scope than the first and which not only contains descriptions of full analogues, but also includes several pharmacological analogues. IUPAC Chemistry International 2010 July-August  Related terms: prototypes,  Regulatory: 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

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

blockbuster drugs: Business of biopharmaceuticals

breakthrough therapies: Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).  US FDA, Therapies

combination products: Regulatory

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,

Critical path:  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,    

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. 

developability small molecule: Using compounds occupying four distinct clog P/molecular weight regions that define optimal and sub-optimal chemical space, and a developability score derived from solubility, permeability, protein binding and 3A4 inhibition screening data, OPLS regression models were constructed to determine which physico-chemical properties were most correlated with developability. The results suggested that whilst certain molecule properties were important for developability across all chemical space, such as [clog D + aromatic ring count], [clog D + (aromatic atom count – sp3 carbon count)] and [sp3 carbon count/total carbon count], others such as heteroaliphatic ring count, positive ionisable group count and H-bond donor character exhibited varying degrees of importance depending on the clog P/Mw region.   Increasing small molecule drug developability in sub-optimal chemical space Timothy J. RitchieSimon J. F. MacdonaldSimon PeaceStephen D. Pickett DOI:10.1039/C3MD00003F Med. Chem. Commun., 2013,4, 673-680!divAbstract   See also developability biologics

drug development:
The entire process of bringing a new drug to the market. It includes both preclinical and clinical testing, and regulatory approval. AN: do not confuse with DRUG DISCOVERY which is the process of finding chemicals for potential therapeutic use MeSH 2019

the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes pre-clinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug.[1][2]   Wikipedia accessed 2018 Nov 10     Related terms: attrition, hit to lead, lead optimization, lead validation

drug discovery:  the process by which new candidate medications are discovered. Historically, drugs were discovered through identifying the active ingredient from traditional remedies or by serendipitous discovery. Later chemical libraries of synthetic small moleculesnatural products or extracts were screened in intact cells or whole organisms to identify substances that have a desirable therapeutic effect in a process known as classical pharmacology. Since sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins, it has become common practice to use high throughput screening of large compounds libraries against isolated biological targets which are hypothesized to be disease modifying in a process known as reverse pharmacology. Hits from these screens are then tested in cells and then in animals for efficacy. Modern drug discovery involves the identification of screening hits, medicinal chemistry and optimization of those hits to increase the affinityselectivity (to reduce the potential of side effects), efficacy/potencymetabolic stability (to increase the half-life), and oral bioavailability. Once a compound that fulfills all of these requirements has been identified, it will begin the process of drug development prior to clinical trials.  Wikipedia accessed 2018 Nov 10
 Related terms: drug development,  drug discovery chemistry    target validation

Discovery on Target Sept 16-19, 2019 • Boston, MA Program |  novel drug targets and technologies for small molecules and biologics
Discovery on Target

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

A pipeline is best defined as what the company potentially has to offer for a product. Key word: potentially. It is 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 
Medicines in the pipeline,

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. 

druggable genome: Out of the nearly 20,000-25,000 protein-coding genes in the human genome, approximately 3,000 are estimated to be part of the druggable genome, the subset of genes expressing proteins with the ability to bind drug-like molecules. Yet, less than ten percent of the druggable proteins are currently targeted by FDA-approved drugs.  A significant number of those remaining are understudied and will be the focus of the implementation phase of the IDG. Illuminating the druggable genome

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

a term used in drug discovery to describe a biological target (such as a protein) that is known to or is predicted to bind with high affinity to a drug. Furthermore, by definition, the binding of the drug to a druggable target must alter the function of the target with a therapeutic benefit to the patient. The concept of druggability is most often restricted to small molecules (low molecular weight organic substances)[1] but also has been extended to include biologic medical products such as therapeutic monoclonal antibodies. Wikipedia accessed 2019 June 24

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

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 
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


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., Independent Institute, 2003  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 companies 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

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: The development of 'follow on' or 'me too' drugs — generally defined as a drug with a similar chemical structure or the same mechanism of action as a drug that is already marketed — has attracted contrasting views. Some have argued that follow-on drugs often provide useful alternative or enhanced therapeutic options for patients or patient subpopulations, as well as introducing price competition. Others, however, consider that the development of such drugs is duplicative and that the resources needed would be better directed elsewhere. Implicit in some of this criticism is the notion that the development of me-too drugs is undertaken after a first-in-class drug has made it to market and proved commercially successful. In this Perspective, using analysis of development and patent filing histories of entrants to new drug classes in the past five decades, we provide new evidence that the development of multiple new drugs in a given class is better characterized as a race, rather than the imitation of successful products. Joseph A. DiMasi  & Laura B. Faden  Competitiveness in follow-on drug R&D: a race or imitation?  Nature Reviews Drug Discovery volume10, pages23–27 (2011)

generic drug: pharmaceutical drug that has the same chemical substance as the drug that was originally developed, patented and innovated. Generic drugs are allowed for sale after the expiry of the patent of the original drugs. Because the active chemical substance is the same, the medical profile of generics is believed to be equivalent in performance.[1][2] The generic drug has the same Active Pharmaceutical Ingredient (API) as the original, but it may differ in characteristics such as manufacturing process, formulationexcipients, color, taste, and packaging.[2][3] … "Branded generics" on the other hand are defined by the FDA and NHS as "products that are (a) either novel dosage forms of off-patent products produced by a manufacturer that is not the originator of the molecule, or (b) a molecule copy of an off-patent product with a trade name."[10]    Wikipedia accessed 2018 Nov 10  Related term: Biologics biosimilar

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 Narrower terms: Gleevec, Herceptin

GLP Good Laboratory Practice: Regulatory

HealthCommons:  a coalition of parties interested in changing the way basic science is translated into the understanding and improvement of human health. Coalition members agree to share data, knowledge, and services under standardized terms and conditions by committing to a set of common technologies, digital information, principals, research materials, contracts, workflows, and software. These commitments ensure that knowledge, data, materials, and tools can move seamlessly from partner to partner across the entire drug discovery chain. This, in turn, enables participants to offer standardized services (ranging from simple molecular assays to complex drug synthesis) in directories that others can discover and integrate into their own processes to expedite development—or assemble like LEGO blocks to create new services.

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

Innovative Medicines Initiative IMI: a European initiative to improve the competitive situation of the European Union in the field of pharmaceutical research. The IMI is a joint initiative (public-private partnership) of the DG Research of the European Commission, representing the European Communities, and the European Federation of Pharmaceutical Industries and Associations (EFPIA). IMI is laid out as a Joint Technology Initiative within the Seventh Framework Programme.[1][2][3][4][5][6][7][8]   Wikipedia accessed 2018 Nov 10

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

me too drugs: See follow-on drug

mechanism of action: Pharmacogenomics

microdosing: a technique for studying the behaviour of drugs in humans through the administration of doses so low ("sub-therapeutic") they are unlikely to produce whole-body effects, but high enough to allow the cellular response to be studied. This is called a "Phase 0study" and is usually conducted before clinical Phase I to predict whether a drug is viable for the next phase of testing. Human microdosing aims to reduce the resources spent on non-viable drugs and the amount of testing done on animals.  Less commonly, the term "microdosing" is also sometimes used to refer to precise dispensing of small amounts of a drug substance (e.g., a powder API) for a drug product (e.g., a capsule),[1] and when the drug substance also happens to be liquid this can potentially overlap what is termed microdispensing. For example, psychedelic microdosing.[2] Wikipedia accessed 2018 Nov 10

Almost half of new drugs fail at the transition from animal to human trials. Human microdosing points the way to smarter drug development and may be the answer to what has been perceived as a productivity crisis in the industry.  By testing only 1% of a pharmacological dose in humans, failures can be identified much earlier in the development process – at Phase 0. This approach has proven to be successful in ADME prediction, helping scientists identify which candidates merit further development.  Microdosing technology can also be used to determine absolute bioavailability, thus aiding drug developers to assess pharmacodynamics and physiological activity. Gathering scientists together to discuss this new and important tool certainly seems needed in order to promote faster, more efficacious drug development.  Using microdosing shows promise of reducing time spent on drugs destined to fail, and also cutting down on the costs associated with testing. In addition, human microdosing at Phase 0 will mitigate the need for testing in animals, and can also help to determine the best animal models to use. Microdosing studies have become possible due in large part to the technical advances of detection instruments. Related term: phase zero, phase 0

molecular therapeutics: Biologics
NCE New Chemical Entity: Regulatory

Oligonucleotide & Precision Therapeutics  March 26-28, 2019 Cambridge, MA Program advances in next-generation oligonucleotide therapies throughout the drug development process.

Oligonucleotide Discovery & Delivery  March 26-27, 2019 Cambridge, MA  Program | detailed case studies on antisense, RNA, aptamer and oligonucleotide conjugates  .

orphan drugs: The Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug. FDA

May be defined as :Drugs that are not developed by the pharmaceutical industry for economic reasons but which respond to public health need.  Actually, the indications of a drug may also be considered as ' orphan ' since a substance may be used in the treatment of a frequent disease but may not have been developed for another, more rare indication. In fact, three cases may arise :  Products intended to treat rare diseases : These products are developed to treat patients suffering from very serious diseases for which no treatment, or at least a satisfactory one, has so far been available. These diseases affect only a small proportion of the population (less than one person per 2,000 in Europe), most often at birth or in infancy. The number of rare diseases for which no treatment is currently available is estimated to be between 4,000 and 5,000 world-wide. Twenty-five to 30 million people are reported to be affected by these diseases in Europe. Products withdrawn from the market for economic or therapeutic reasons : For example, thalidomide widely much used as a hypnotic drug some years ago and was then withdrawn from the market when its high teratogenic (triggering fetal malformations) risk was discovered. However this drug showed very interesting analgesic proprieties in diseases such as leprosy or lupus erythematosus. They are diseases for which no satisfactory treatment has been available. Products that have not been developed :either because they are derived from a research process that cannot be patented ; or because they concern important markets which are, however, not creditworthy (see the text Orphan drugs for Third-World countries). Orphanet About orphan drugs  Related term: rare diseases

orphan products: Regulatory
outsourcing: Business of biotechnology & pharmaceuticals

Over-the-counter (OTC) drugs:  medicines sold directly to a consumer without a prescription from a healthcare professional,[1] as opposed to prescription drugs, which may be sold only to consumers possessing a valid prescription. … OTC drugs are usually regulated by active pharmaceutical ingredients (APIs), not final products. By regulating APIs instead of specific drug formulations, governments allow manufacturers freedom to formulate ingredients, or combinations of ingredients, into proprietary mixtures.[2]   Wikipedia accessed 2018 Nov 10

Over-the-counter medicine is also known as OTC or nonprescription medicine. All these terms refer to medicine that you can buy without a prescription.  FDA

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

Phase zero, Phase O: a recent designation for optional exploratory trials conducted in accordance with the United States Food and Drug Administration's (FDA) 2006 Guidance on Exploratory Investigational New Drug (IND) Studies.[3] Phase 0 trials are also known as human microdosing studies and are designed to speed up the development of promising drugs or imaging agents by establishing very early on whether the drug or agent behaves in human subjects as was expected from preclinical studies. Distinctive features of Phase 0 trials include the administration of single subtherapeutic doses of the study drug to a small number of subjects (10 to 15) to gather preliminary data on the agent's pharmacokinetics (what the body does to the drugs).[4] A Phase 0 study gives no data on safety or efficacy, being by definition a dose too low to cause any therapeutic effect. Drug development companies carry out Phase 0 studies to rank drug candidates in order to decide which has the best pharmacokinetic parameters in humans to take forward into further development. They enable go/no-go decisions to be based on relevant human models instead of relying on sometimes inconsistent animal data. Wikipedia accessed 2018 Nov 10  Related terms: microdosing   Biomarkers type 0 biomarker  

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. 
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 

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 

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

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 the lead optimization process.)  Insight Pharma Reports, Backup Compound Strategies: Best Practices for Reducing Phase II Risk, 2007

prototypes drug:  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

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

reverse pharmacology: In the field of drug discovery, reverse pharmacology [1][2][3] also known as target-based drug discovery (TDD),[4] a hypothesis is first made that modulation of the activity of a specific protein target will have beneficial therapeutic effects. Screening of chemical libraries of small molecules is then used to identify compounds that bind with high affinity to the target. The hits from these screens are then used as starting points for drug discovery. This method became popular after the sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins. This method is the most widely used in drug discovery today.[5] Differently than the classical (forward) pharmacology, with the reverse pharmacology approach in vivo efficacy of identified active (lead) compounds is usually performed in the final drug discovery stages. Wikipedia accessed 2018 Nov 19

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

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

ultra-orphan drugs: In the U.S., the number of patients used for the designation of orphan drugs is <200,000; that is, 1 in 1500 people [12]. In the EU, the number of patients used for the designation of orphan drugs is ≤5 per 10,000 people, i.e., 1 in 2000 people; [13] in actual terms for some orphan drugs the number is often less than 1 per 100,000 people [14]. In Japan, the designation for orphan drugs targets diseases with <50,000 patients [15], which corresponds to 1 in 2600 people. Health Science Council of MHLW defines ultra-orphan drugs as pharmaceuticals for diseases that affect <1000 people [16] Points to consider: efficacy and safety evaluations in the clinical development of ultra-orphan drugs  Kojiro Maeda, Masayuki Kaneko, Mamoru Narukawa, Teruyo Arato, Orphanet Journal of Rare Diseases201712:143  Published: 23 August 2017   Broader term: orphan drugs

World Preclinical Congress  now World Pharma Week June 17-21, 2019 • Boston, MA   

Drug discovery & development resources
IUPAC International Union of Pure and Applied Chemistry, Glossary of terms in Biomolecular Screening 2011 
IUPAC International Union of Pure and Applied Chemistry, Nomenclature in laboratory robotics and automation, 1994
MeSH Medical Subject Headings, PubMed 
Nature Drug Discovery gateway, Nature Publishing Group

Drug discovery & development Conferences
Discovery on Target
Molecular Medicine Tri Conference
World Pharmaceutical Congress WPC

How to look for other unfamiliar  terms

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

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