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Drug discovery & development: Genomics, bioinformatics & beyond
Mary Chitty
  mchitty@healthtech.com 617-630-1316    not being updated

Databases   Journals   Pharmacogenomics    Toxicogenomics  Clinical trials 

Drug discovery and development Overviews & introductions

Drug Discovery and Development Databases
What really belongs here?
A major challenge is database interoperability and integration from all the disciplines involved.

Medline is being extensively used for genomic text mining.
Project Arrowsmith, UIC, UC http://arrowsmith.psych.uic.edu/arrowsmith_uic/

Compendium of free, public biomedical text mining tools available on the web  http://arrowsmith.psych.uic.edu/arrowsmith_uic/tools.html

See also  Databases   Genomic  and proteomics   Chemistry   Bioinformatics   Business

Drug Discovery and Development Journals  See also Journals  Molecular Medicine   Pharmacogenomics  Toxicogenomics

Anti-Cancer Drugs, Lippincott, 1990-  http://www.anti-cancerdrugs.com/pt/re/anticd/home.htm;jsessioni...1  Reports both clinical and experimental results related to anti- cancer drugs, and welcomes contributions on anti- cancer drug design, drug delivery, pharmacology, hormonal and biological modalities and chemotherapy evaluation. Fast publication of innovative investigations on therapeutic agents against cancer, aims to stimulate and report research on both toxic and non- toxic anti- cancer agents. Covers both conventional cytotoxic chemotherapy and hormonal or biological response modalities such as interleukins and immunotherapy. 

BMC Pharmacology, BioMedCentral, 2001-  http://www.biomedcentral.com/bmcpharmacol/ Original research articles in all aspects of the design, uses, effects, and modes of action of therapeutic agents.

BioDrugs, Adis, 1997- Developments in the clinical application of biotechnology for the treatment of human disease, clinical development and therapeutic application of biotechnology- based pharmaceuticals, diagnostic products, and innovative technologies, novel drug delivery systems, protein/ peptide therapeutics, monoclonal antibodies and antibody fragments, cytokines and cytokine receptors, recombinant DNA and gene regulation technology, gene therapy, antisense oligonucleotides, catalytic RNA, stem cell therapies, nuclear transfer, high throughput drug screening, phage display, drug target validation, glycolated and pegylated therapeutics, pioneering technologies in drug design and development.  Impact factor 1.24

Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals,  Taylor & Francis, 1996-http://taylorandfrancis.metapress.com/app/home/journal.asp?wasp=9d47fa0ec79e41  Biomarkers of effect: including measures of endogenous substances or parameters indicative of biological change such as alteration in enzymes in tissues or body fluids. Biomarkers of susceptibility or sensitivity: including genetic factors and changes in receptors which alter the susceptibility of an organism to exposure to a chemical substance. Biomarkers of response: All three types of markers may be either in vivo or in vitro and will apply to any biological system, not just human or mammalian.

Biopharmaceutics and drug disposition, Wiley, 1979- http://www3.interscience.wiley.com/cgi-bin/jhome/2073 Studies in biopharmaceutics, drug disposition and pharmacokinetics, especially those which have a direct relation to the therapeutic use of drugs. This includes human pharmacological studies, and therapeutic response and toxicity related to plasma and tissue concentrations of drugs and their metabolites. Research on factors affecting the disposition of the clinical response to drugs, and on the design of drug dosage regimens and the treatment of overdose, based on pharmacokinetic principles, are accepted. Papers on analytical methodology, in vitro drug metabolism, and on animal models are also published, provided that either they facilitate the preceding types of investigation, or they are related to the use of drugs in man.

Cancer Gene Therapy, Nature Publishing, 1994- http://www.nature.com/cgt/ Results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy as applied to cancer research.  Case reports, preliminary communications, review articles, Industry perspective (descriptions of the newest technology being developed in the corporate sector)., Impact factor 2.9

Comparative Biochemistry and Physiology - Part C: Toxicology & Pharmacology

Current opinion in Investigational Drugs, Thomson Current Drugs, 2000- http://thomsoncurrentdrugs.com/coid/ Six therapeutic areas surveyed (twice a year): Anti- infectives, Anti- inflammatories, Cardiovascular, Endocrine and metabolic, Central and peripheral nervous system, Oncological reviews and drug evaluations. 

Current drug discovery, Thomson Current Drugs, date-  http://www.currentdrugdiscovery.com/index.html  Covers topics such as proteomics, pharmacogenomics, lab automation, virtual screening, outsourcing, database mining, intellectual property, drug delivery, clinical trials, regulatory affairs, portfolio management and ethics.

Current Pharmaceutical Design, Bentham, 1995- http://www.bentham.org/cpd/index2.html All aspects of current research in rational drug design. Each  issue is devoted to a single major therapeutic area. Each thematic issue covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism. 

Drug Discovery Today, Elsevier, 1996- http://www.drugdiscoverytoday.com/  Cutting- edge R&D technologies, the impact of revolutions in genomics, proteomics, informatics, systems biology, chemistry and biology, advanced therapeutic approaches, vaccines, diagnostics, clinical trials, new business strategies, and novel drug and gene delivery systems. 

Gene Therapy, Nature Publishing, 1994- http://www.nature.com/gt/ Research and clinical applications of the new genetic therapy techniques currently being developed.  All aspects of gene therapy as applied to human disease including preclinical animal experiments, novel platform technologies for gene transfer and gene expression analysis.  Impact factor 5.6

Genetic Vaccines and Therapy, BioMedCentral, 2003-  http://www.gvt-journal.com/   Open access online journal that aims to apply new knowledge about genetics in treating human disease. Will consider reports of clinical and basic research in the identification of pathogen genes for vaccines and gene targets for therapy, novel gene transfer vectors and methods of gene delivery, experimental models and mechanisms of immunoprotection, and treatment of acquired and inherited genetic deficiencies. DNA vaccines and gene therapy are of the highest interest ...  the basic problems of cell growth and division, signal transduction and cell death - some of the most profound areas of modern biology. As the basic unit of biological activity, the gene is the logical candidate for such studies. While it is important to study normal gene function, the mutant or aberrant behaviour of the gene often tells us more about the underlying biological process; and from that we may devise ways to prevent or cure the disease.

Journal of Gene Medicine, Wiley, 1999-http://www3.interscience.wiley.com/cgi-bin/jhome/10009391  Print and electronic journal on the science of gene transfer and its clinical applications. Will consider articles on all aspects of gene therapy including design and production of vectors, research into the mechanisms underlying gene transfer, preclinical studies including animal models, developmental aspects (large- scale production, toxicology) and clinical trials. The editors particularly welcome articles dealing with the methodological aspects of gene transfer in vivo, notably in the context of human studies. Articles addressing more fundamental biological issues which could open up avenues for more effective gene transfer are also welcome. 

Molecular Pharmaceutics, American Chemical Society, 2004- http://pubs.acs.org/journal/mpohbp   Will concentrate on "the rapidly advancing molecular and mechanistic research in the pharmaceutical and biopharmaceutical fields. Distinct molecular and mechanistic focus emphasizing the chemistry of drug delivery." Drug and delivery system properties, drug transport and metabolism processes, and enzyme and transporter targets for drug delivery and targeting. http://pubs.acs.org/cen/topstory/8112/8112notw9.html

Molecular pharmacology, ASPET, 1965- http://molpharm.aspetjournals.org/  Drug action or selective toxicity at the molecular level, molecular mechanisms. Studies of receptors, signaling, pathways, enzymes, channels, and transcriptional mechanisms. Studies that report the development of novel reagents or technologies that are of broad applicability or yield new molecular insights. Attempts to publish studies with a strong component of biological experimentation, studies involving molecular modeling relevant to drug design or drug activity. also welcome. 

Molecular Therapy, Elsevier, 2000- http://www.elsevier.com/locate/issn/1525-0016  Gene transfer, gene regulation, gene discovery, cell therapy, experimental models, correction of genetic and acquired diseases, and clinical trials. New methodological advances. Official journal of the American Society of Gene Therapy ASGT. 

Nature Reviews Drug Discovery, Nature Publishing, 2002- http://www.nature.com/drugdisc/  In the post- genomic era, the successful translation of basic scientific discoveries into novel therapeutic strategies for the prevention and treatment of disease will depend on integrating all aspects of the drug discovery and development process. Procedures such as target validation, lead- compound identification and optimization, preclinical screening, toxicological profiling, clinical evaluation and regulatory decision-  making will all be relevant to everyone involved in every stage of the pathway. Subjects covered include: Target discovery, Rational drug design, Combinatorial and parallel synthesis, Medicinal chemistry, Key compound classes, Natural products, High-throughput screening, Novel therapeutic approaches to disease states, Microarrays, Bioinformatics and chemoinformatics, Absorption, distribution, metabolism and elimination (ADME), Pharmacokinetics and pharmacodynamics, Pharmacology, Toxicology, Pharmacogenomics and toxicogenomics, Drug delivery, Biopharmaceuticals, Biotechnology, Vaccines, Clinical trial evaluation, Regulatory issues, Pharmacoeconomics 

Pharmaceutical Research, Kluwer, 1984- http://www.kluweronline.com/issn/0724-8741/contents  Innovative research on drug discovery, development, evaluation, and regulatory approval. Small drug molecules, biotechnology products including genes, and genetically engineered cells are an integral part. Preformulation biology and chemistry; Delivery systems and formulation design; Pharmacokinetics, pharmacodynamics and clinical evaluation; Biochemical/ molecular pharmacology of transporters, enzymes and receptors; Genetic variability in drug metabolism, kinetics and response; Molecular targets, proteomics, bioinformatics, and drug design.

Trends in Pharmacological Sciences, Elsevier, 1979- http://www.trends.com/tips/default.htm  Review journal, topics covered range from molecular to behavioural pharmacology, current techniques to theoretical pharmacology.

Drug discovery and development news
BIO newsfeed Genomics, Proteomics & Bioinformatics  http://science.bio.org/genomics.news.html  Other categories include emerging and recurring diseases; bioterrorism & biodefense; BSE, CJD, Mad cow disease; cloning, stem cells & regenerative disease; vaccines & therapeutics; GMOs, agritech & food, bioethics, biotech policy & regulations, biotech manufacturing. 

LeadDiscovery’s Daily Updates http://www.leaddiscovery.co.uk/PubMed-dailyupdates.html  Breaking scientific publications with drug discovery potential

Drug discovery & development Websites
IBM Drug Discovery http://www-3.ibm.com/solutions/lifesciences/solutions/discovery.html
IBM Drug development http://www-1.ibm.com/industries/lifesciences/doc/jsp/solarea/develop/ 
IBM Biotech http://www-1.ibm.com/industries/lifesciences/doc/jsp/indseg/biotech/

Pharmacogenomics
Definitions
Pharmacogenomics introductions & overviews

Pharmacogenomics databases
International HapMap Project
http://www.hapmap.org/  A partnership of scientists and funding agencies from Canada, China, Japan, Nigeria, the United Kingdom and the United States to develop a public resource that will help researchers find genes associated with human disease and response to pharmaceuticals.

Note on haplotypes: Genes tend to travel in packs.  With any luck this will make pharmacogenomics less likely to totally fragment the pharmaceutical landscape.

SNP Consontium

Pharmacogenomics journals
American Journal of Pharmacogenomics, Adis, 2001-

Pharmacogenomics, Ashley Publications, 2000-  http://www.pharmaco-genomics.com/    Resources and technology, developments, corporate capabilities and research, relationship between genotype and drug response and emerging technologies.

Pharmacogenomics Journal, Nature Publishing, 2001- http://www.nature.com/tpj/ Scope: Clinical applications, Effects of genetic variability on drug toxicity and efficacy, Identification and functional characterization of polymorphisms relevant to drug action, Pharmacodynamic and pharmacokinetic variations and drug efficacy, Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics, Clinical applications of genomic science, Identification of novel genomic targets for drug development, Potential benefits of pharmacogenomics.

more journals: pharmacology and drug metabolism

Toxicogenomics  
May overlap Using Pharm Lit Section IV  Toxicology
Toxicogenomics Definitions  Toxicogenomics Terminology  Overviews & introductions

Selected Toxicogenomics Databases
Comparative Toxicogenomics Database
, Mount Desert Island Biological Lab http://www.niehs.nih.gov/oc/factsheets/ctd.htm One of the greatest challenges for comparative toxicogenomics is the integration of the vast amount of genomic information being generated for a variety of model organisms. At present, there are several disparate but complementary databases on genomic sequences. Most of these databases provide data on gene and genome sequences for individual animal species. These databases do not provide a means to link the genome data to specific environmental chemicals or to toxicological and biological endpoints. They also do not enable researchers to compare information about potentially similar genes and biological responses across multiple species.

Developmental & Reproductive Toxicology DART National Library Of Medicine, http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?DARTETIC.htm

MIAME for Toxicogenomics, European Bioinformatics Institute, National Center for Toxicogenomics, International Life Sciences Institute http://www.ebi.ac.uk/microarray/Projects/tox-nutri/MIAME-Tox-Checklist.doc

Toxicogenomics Journals & Newsletters
Environmental Health Perspectives: Toxicogenomics, NIEHS, 2003-  http://ehp.niehs.nih.gov/txg/ Quarterly section in Environmental Health Perspectives. Areas covered will include the related disciplines of pharmacogenomics, proteomics, metabonomics, molecular epidemiology, translational aspects of genomic research, and molecular medicine. 

European Journal of  Genetic and Molecular Toxicology, European Environmental Mutagen Society, 1997- http://www.swan.ac.uk/cget/ejgt/issues.htm  Online journal

Journal of Biochemical and Molecular Toxicology, Wiley, 1998- http://www.wileyeurope.com/WileyCDA/WileyTitle/productCd-JBT.html  Molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. Effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.  [formerly Journal of Biochemical Toxicology]

Toxicology Mechanisms and methods, Taylor & Francis  http://www.tandf.co.uk/journals/titles/15376516.html Mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. Molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Development, validation, and application of new and existing laboratory methods, techniques, and equipment. Research methods including in vivo studies with standard and alternative species, in vitro studies and alternative methodologies, molecular, biochemical, and cellular techniques, pharmacokinetics and pharmacodynamics, mathematical modeling and computer programs, forensic analyses, risk assessment, data collection and analysis. Was Toxicology Methods

Other  toxicology journals are also relevant.

Toxicogenomics Organizations
National Center for Toxicogenomics, National Institute Environmental Health Sciences  http://www.niehs.nih.gov/nct/

Toxicogenomics Research Consortium http://www.niehs.nih.gov/nct/trc.htm

See also  Journals & newsletters Genomics & proteomics  Bioinformatics   Combichem & chemogenomics   Cheminformatics  Molecular Medicine   Business 

Clinical trials  
Clinical trials informatics defined
The application of informatics approaches to the clinical- evaluation phase of drug development. These approaches can include clinical- trial simulations to improve trial design and patient selection, as well as electronic capturing and storing of clinical data and protocols. The goal is to reduce expenses and time to market.

Clinical trials overviews & introductions
Reengineering the Clinical Research Enterprise,
NIH Roadmap, 2003 http://nihroadmap.nih.gov/clinicalresearch/index.asp

Cancer Clinical Trials: A new national system, NCI http://www.cancer.gov/common/popups/popNationalSystem.htm A fundamental shift is underway in how the National Cancer Institute develops, reviews, conducts, and supports clinical trials…

Clinical Trials Databases
Cancer Biomedical Information Grid caBIG,
National Cancer Institute http://cabig.nci.nih.gov/ A common, extensible informatics platform that integrates diverse data types and supports interoperable analytic tools. This platform will allow research groups to tap into the rich collection of emerging cancer research data while supporting their individual investigations.

Cancer Clinical Trials, NIH http://www.cancer.gov/clinicaltrials

CiteLine TrialTrove http://www.citeline.com/trialtrove.html 

Clinical Trials.gov, NIH, http://www.clinicaltrials.gov/  Federally and privately supported clinical trials for a wide range of diseases and conditions.

National Electronic Clinical Trials and Research (NECTAR) Network: Clinical Research Informatics. http://nihroadmap.nih.gov/initiatives.aspA standardized data system will be developed through a phased planning and development process. The network will allow community- based clinicians from the NIH Clinical Research Associates to participate in important national studies, facilitate the sharing of data and resources, and augment clinical research performance and analysis. Re-engineering the Clinical Research Enterprise, NIH Roadmap Initiatives 

Clinical trials journals and newsletters

Organizations
CDISC Clinical Data Interchange
http://www.cdisc.org/ An open, multidisciplinary, non-profit organization committed to the development of industry standards to support the electronic acquisition, exchange, submission and archiving of clinical trials data and metadata for medical and biopharmaceutical product development.

Center for Drug Development Science, Georgetown Univ. Medical Area, Washington DC http://www.georgetown.edu/research/cdds/ 

Society for Clinical Trials http://www.sctweb.org/

Clinical trials reports
Armitage Report,
Clinical Trials Program Review Group, 1997 http://www.cancer.gov/common/popups/popNationalSystem.htm

CONSORT statement: Revised recommendations for improving the quality of reports of parallel group randomized trials, David Moher et. al, BMC Medical Research Methodology 2001, 1:2
http://www.biomedcentral.com/1471-2288/1/2

Clinical Trials terminology

Other Information resources Genomics, proteomics   Drug discovery & development top;   Chemical genomics Toxicogenomics Bioinformatics   Cheminformatics     Technologies   Molecular Medicine    Business 

What are genomics and proteomics? chemical genomics?  pharmacogenomics?   toxicogenomics?  What are bioinformatics? cheminformatics?  informatics? 

 

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