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

Drug discovery & development Map: Finding guide to terms in these glossaries  Glossaries & Taxonomies Site Map   Therapeutic areas: covers cancer & oncology, cardiovascular, CNS & neurology, Immunology, Infectious diseases, and Inflammation
Related glossaries include   Drug Safety, Pharmacovigilance & Post Marketing Surveillance    Drug targets     Pharmacogenomics  
Business  Business of biopharmaceuticals   Clinical trials, drug, device & diagnostics approvals   Finance & Pharmacoeconomics    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.  [move to assays]

adjuvants - novel vaccines: See under delivery systems: vaccines

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

animal models: Insight Pharma Report forthcoming 2009    See also Model organisms

antibody therapeutics: Though therapeutic antibodies have achieved phenomenal success, many challenges stand waiting to be addressed.  This meeting will explore some of the successes while reviewing the inherent obstacles that can block progression into the clinic with an eye for ferreting out the optimal protocols and highlighting the best technologies that support development. The focus for the meeting is the momentous task of designing a soluble and glycosylated therapeutic antibody that can be delivered efficaciously and penetrate into the tissue or tumor. 
Antibodies January 11-12, 2010 • Coronado, CA  Program | Register | Download Brochure

See also monoclonal antibodies, protein therapeutics 

antibodies: Therapeutic and diagnostic antibodies continue to make in inroads in biomedicine, but the successful application of these products requires smart discovery and development.  This conference will explore the latest methods to overcome challenges and open new opportunities for making these valuable proteins viable.
   Engineering antibodies

Antibody optimization
PEGs Protein Engineering Summit May 2010,Boston MA

assays: Assays & screening  

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

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

bi-specific antibodies: interest in bispecific and multivalent antibodies has been renewed because of advances that now allow them to be manufactured in a stable and reliable manner.  This has opened up the field to a multitude of approaches for creating bispecific antibodies against a variety of targets.  The decision-making process about when a bispecific or multiclonal approach should be used, and what mechanism is likely to be the most effective against a given indication. PEGs Protein Engineering Summit May 2010,Boston MA     Bi-specific antibodies

bioanalytical challenges:   See ligand binding assays

biotherapeutic targets: See ligand binding assays

blockbuster drugs: Business of biopharmaceuticals

cell therapeutics, cellular therapy: Stem cells  See also high content assays

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:  Fixed-Dose and Co-Packaged combinations provide novel business opportunities for companies to leverage their existing products and intellectual property. However, they also offer unique development, regulatory and commercial challenges. This conference will focus on the practical interplay between combination therapy forefront research, development challenges, and commercial and partnering strategies, as well as the implications for successful market realization. Combination Drug Therapies  April 13-14, 2010 • Philadelphia, PA Program | Register | Download Brochure 

Insight Pharma Reports forthcoming 2009

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: Molecular diagnostics

cytokine-based therapeutics: Topics 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 2008, San Francisco, CA  Order conference CD

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: In silico & Molecular modeling,   Pharmaceutical biology

delivery systems - vaccines: Sessions include adjuvant breakthroughs & successes, Toll Like Receptors TLRs  Novel Vaccines: Adjuvants & Delivery systems Aug 2009 Providence RI Order CD 

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; about 538,000 Nov 20, 2009

diagnostics, molecular: Molecular Diagnostics

disease targets: Drug Targets

docking: In silico & molecular modeling

drug: Drug approvals

drug delivery:  Delivery of Biologics February 3-5, 2010 • San Francisco, CA Program | Register | Download Brochure

drug design: Chemoinformatics

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:  Discovery on Target, Nov 2009 Boston MA  Order CDs   
PEGs Protein Engineering May 2010 includes 

Cambridge Healthtech upcoming conferences

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

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: With drug development cycles requiring an average of 15 years and US $800 million to bring a single drug to market, drug repositioning efforts, which create alternative development routes for compounds that failed to meet their clinical endpoints but met safety milestones, are becoming an important part of the strategy for pharmaceutical companies desperate to fill lean late-stage development pipelines and keep costs down. Repositioning approaches are also being employed for existing drugs to identify alternative uses or new indications for them. In the past few years, new technologies, improved genomic information and high-throughput methods have made it possible to quickly and economically re-examine advanced drug candidates for therapeutic activity against other diseases. Specialized companies are also emerging with new methods and expertise in  assisting pharmaceutical developers in turning failed drug candidates from one therapeutic area into successful treatments in another. These methods involve screening a compound against new targets, or investigating a given target against new indications. Repurposing or repositioning represents both a faster and less risky route to development and an important strategy to extend the applications range and patent life of a drug. Drug repositioning, Oct 2009, Boston MA  Order CD

also known as drug repurposing: Insight Pharma Report forthcoming 2009 

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).  Druggable = about 129,000 Nov 20, 2009

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 

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

Google Mar. 5, 2004 = drug-like: about 61,500; Apr 6, 2007 about 523.000; about 360,000 Nov 20, 2009
drug-likeness Mar 5, 2004 about 592, Apr 6, 2007 about 22,200; about 26,000 Nov 20, 2009
druglike Mar 5, 2004 about 976, Apr 6, 2007 about 26,700; about 384,000 Nov 20, 2009

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:  Optimizing Biologics Formulation Development: Managing the Early Formulation-Manufacturing Interface to Overcome Stability, Processing and Manufacturing Challenges and Achieve Fit for Purpose Drug Product” covers the latest trends and challenges in biologics formulation and development with a focus on: improving time to market via early formulations and characterization, overcoming aggregation challenges, utilizing enabling analytical methodologies, using experimental design and high-throughput principles, and improving convenience and compliance through delivery technologies.  Optimizing Biologics Formulation Development January 11-12, 2010 • Coronado, CA  Program | Register | Download Brochure  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. 

Formulation & drug delivery upcoming conferences 
 Optimizing Biologics Formulation             Protein Aggregation   January 13 -14           Lyophilization & Spray Drying 2010  January 14-15
Development        January 11 - 12             Coronado CA        Program | Register | Download Brochure  
                         

Order CDs from past Drug delivery conferences including:   Aug 18-19, 2009 • Providence, RI  Program | Register | 
June 8-9, 2009 Tackling RNAi
June 8-0  2009 San Francisco Program
 Delivery San Francisco, CA

See also drug delivery

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: The need to predict and counter immunogenicity in therapeutic antibodies and proteins is a serious concern and it remains a significant challenge to address immunogenic properties in drug candidates.  Bioanalytical assays need to be developed and validated to support the development of immunogenicity protocols. PEGs Protein Engineering Summit May 2010,Boston MA  Immunogenicity  

Non-clinical testing is currently used to screen for immunogenicity and subsequent selection of suitable non-immunogenic molecules. Additionally investigators are developing platforms for non-immunogenic drugs which focus on reducing aggregation and optimising formulation, and even by generating products that fail to bind to MHC and therefore lack the immunogenicity-promoting T cell epitopes. Immunogenicity prediction & reduction 2009 Oct Philadelphia PA  Order CD

Current concerns regarding immunogenicity are focussed on accurate per-clinical assessment and the clinical significance. White papers offering advice have been produced by the experts but despite the obvious help they provide, difficulties and uncertainties remain.  Key amongst these are the challenges of dealing with free drug in the assay, the difficulties of obtaining true positive results, and the constant dilemma of how to satisfy the regulatory authorities while the guidance remains undefined. Immunogenicity assessment & clinical relevance 2009 Oct Philadelphia PA  Order CD

Immunotherapeutics & Vaccines Aug 2009 Providence RI   Order CD

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

in silico screening: See virtual screening Chemoinformatics

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  erectile dysfunction, baldness, and some aging therapies..  

ligand binding assays: One of the key reasons Protein Therapeutics have achieved significant success stems from their ability to bind to specific targets, such as receptors or cell surface proteins, with high affinity. As Protein and other Macromolecule Therapeutics become more complex, bioanalytical challenges have increased, especially for multi-domain and multi-valent biopharmaceuticals.  Ligand Binding Assays (LBAs), which indirectly measure reactions with the binding reagents, continue to be the preferred method of analyzing macromolecule therapeutics.  However, to date no clear guidance or consensus exists that outlines how to consistently monitor and validate specificity and selectivity for ligand binding assays, and what methods are necessary to differentiate between “free” and “total” therapeutic.  Additionally, there is a need to establish criteria for reagent quality, lot-to-lot consistency, and maintaining a sustainable reagent supply.  Bioanalytical challenges for optimizing protein therapeutics    PEGs Protein Engineering Summit May 2010,Boston MA 
 

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, drug-likeness, pharmaceutically tractable, tractable targets

mechanism of action: Pharmacogenomics

medicinal chemistry: Chemistry & biology 

microdosing:  Pharmacogenomics  Related term: phase zero, phase 0

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

molecular therapeutics: Current Opinion in Molecular Therapeutics is published bimonthly and covers the broad field of molecular medicine, including viral and non-viral gene therapy, oligonucleotides, peptide therapeutics, antibody approaches, molecular vaccines, and the technologies underlying genomics and proteomics. Scope note: Current Opinion in Molecular Therapeutics, BioMedCentral http://www.biomedcentral.com/curropinmolther/ 

monoclonal antibodies: Monoclonal antibodies represent about half of all biologics in development, with more than 150 compounds currently in clinical trials.  However, the attrition rate of monoclonal antibodies has been higher than for other biologics.  While early studies in pre-clinical settings have been encouraging, the predictability and confirmation of these same findings in humans has been difficult. The reasons for this may include: 1) target antigen properties; 2) antibody design; 3) PK and PD properties; 4) limited species cross reactivity (limited availability of suitable animal models); 5) appropriate translation of pre-clinical data to pick FIH dose; and 6) accurate identification of patients who could benefit from target therapy.  Pre-clinical clinical development  PEGs Protein Engineering Summit May 2010,Boston MA

In the more than 30 years since the first process for creating monoclonal antibodies, or mAbs, was introduced, they have remained a centerpiece of the growing biotechnology industry. Twenty-four therapeutic mAbs have been approved, several of which have attained blockbuster status, with sales reaching the coveted billion-dollar mark and well beyond. Two drugs, Remicade and Rituxan, generated sales of about $4 billion each in 2006, and global sales for this entire portfolio approached $20 billion in that year. Insight Pharma Reports  Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment, 2007

A single species of immunoglobulin molecules produced by culturing a single clone of a hybridoma cell. MAbs recognize only one chemical structure, i.e., they are directed against a single epitope of the antigenic substance used to raise the antibody. [IUPAC Biotech] 

Antibodies produced by clones of cells such as those isolated after hybridization of activated B lymphocytes with neoplastic cells. These hybrids are often referred to as hybridomas. MeSH, 1982

Broader term: antibody; Related terms: clinical antibodies, cloning, hybridoma, fully humanized antibodies, polyclonal antibodies,  recombinant antibodies,  therapeutic antibodies, polyclonal antibodies 

multiplex assays: Assays  See also microarrays

NCE New Chemical Entity: Drug approvals

niche busters: with increased competition from generic drugs, sky-rocketing costs of marketing blockbusters and declining support from regulators, pharmaceutical companies are starting to shift their growth strategies away from blockbuster drugs and on to niche-centric drugs. Niche-busters, as they are being labeled, face less competition and lower marketing costs. The value of theses niche-buster drugs grows significantly when an increased focus on research and development yields faster development times. Champions 2.0, Issy Goldwasser, Symyx Technologies,  BioIT World 2007 http://www.bio-itworld.com/issues/2007/march/champions/symyx/ 

NME New Molecular Entity: Drug approvals

orphan products: Drug approvals

outsourcing: Business of biotechnology & pharmaceuticals

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

peptide therapeutics:  As potential therapeutics, peptides offer several advantages over small molecules (increased specificity) and antibodies (small size). However, delivery and sensitivity to serum and tissue proteases coupled with short serum half-life have remained major therapeutic stumbling blocks.  
  Peptide Therapeutics January 14-15, 2010 • Coronado, CA  Program  Register 

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: 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

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 

Pipeline Success Summit 

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. 

Google = about 507,000 preclinical development July 31, 2007  about 430,000 Nov 20, 2009
Google = about 41,400 preclinical drug development July 31, 2007; about 18.600 Nov 20, 2009

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

Related terms: Drug safety & pharmacovigilance

preclinical/clinical development - novel vaccines: Sessions include immune response biomarkers, enhancing the immune response: preclinical case studies; Preclinical/Clinical Development of Immunotherapies & Vaccines Aug 2009 Providence RI

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 outsourcing: Business of biotechnology & pharmaceuticals

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 aggregation: Understanding and Overcoming Analytic, Formulation, Manufacturing, and Regulatory Challenges” covers the latest trends and challenges with a focus on: understanding and controlling protein aggregation, improving detection and quantitation of aggregates, analyzing subvisible and visible particles with various techniques, utilizing complimentary technologies for characterization, developing approaches for rational design/protein engineering of aggregation-resistance for proteins, understanding aggregates as an inducing factor in immungenicity, improving structural analysis and modeling to predict protein aggregation, and understanding the impact of primary sequence and refolding potential on aggregation. Protein Protein Aggregation January 13-14, 2010 • Coronado, CA Program | Register | Download Brochure  

The study and prevention of protein aggregation and its consequences represents one of the most demanding tasks in biomedical research and pharmaceutical manufacturing today. Whether one’s interests lie in protein characterization or analytics,  the study of protein aggregation-induced adverse effects or immunogenicity, or you work in formulation and process development for protein-based therapeutics, “Protein Aggregation in Biopharmaceutical Products” will provide a comprehensive real-world perspective on this challenging arena. Protein Aggregation  
PEGs Protein Engineering Summit May 2010,Boston MA  

protein delivery: Increasing the success rate of novel therapeutic entities involves anticipating drug delivery routes and considerations early in discovery.  Innovative drug delivery approaches will 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.   Engineering Protein Therapeutics for Delivery PEGs  April  2009, Boston MA order CD

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: Creating protein-based therapeutics that accomplishes their mission of safely delivering efficacious compounds to human targets is a complex challenge. Proteins’ innate qualities make the task difficult, and unforeseen variables typically add additional complications. However, the proven success of antibodies and protein-based therapeutics make them an important – and promising – class of drugs with more than one hundred approved biopharmaceutical products generating revenue of more than US$56 billion. Peptide and Protein-based Therapeutics Meeting the challenges of delivery safety & efficacy PepTalk  January  2010, San Diego CA  

Once a rarely used subset of medical treatments, protein therapeutics have increased dramatically in number and frequency of use since the introduction of the first recombinant protein therapeutic — human insulin — 25 years ago. Protein therapeutics already have a significant role in almost every field of medicine, but this role is still only in its infancy. Protein therapeutics: a summary and pharmacological classification, Benjamin Leader, Quentin J. Baca & David E. Golan Nature Reviews Drug Discovery 7, 21-39 (January 2008) | doi:10.1038/nrd2399 

See also antibody therapeutics, protein aggregation

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

R&D informatics: Data management, integration * knowledge management Adopting R&D Informatics Systems February 3-5, 2010 • San Francisco, CA Program | Register | Download Brochure    

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

Recombinant Proteins January 13-14, 2010 • Coronado, CA  Program | Register | Download Brochure

repositioning, repurposing: See drug 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

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; small molecule libraries

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

Ultra High Throughput screening uHTS: Assays & screening

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 June 2010, Philadelphia, PA 
has tracks on   Monitoring Cardiotoxicity and Drug Safety   Nephrotoxicity & Drug Safety   Expanding Impact of New Animal Models in Drug Safety    Hepatotoxicity and Drug Safety       Risk Management and Drug Safety    Early Assessments for Nephrotoxicity

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
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
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.