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Structure-Based Drug Design on Membrane Protein Targets: Human Integral Membrane Protein 5-Lipoxygenase-Activating Protein

Leukotrienes are biologically active lipid metabolites of arachidonic acid that are involved in inflammation and play a significant role in respiratory and cardiovascular disease. The integral nuclear membrane protein 5-lipoxygenase-activating protein (FLAP) is essent ...

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Leveraging SBDD in Protein Therapeutic Development: Antibody Engineering

Antibodies make up the largest, growing segment of protein therapeutics in the pharmaceutical and biotechnology industries. The development or engineering of therapeutic antibodies is based to a large extent on our knowledge of antibody structure and requires sophisticated met ...

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Application of SBDD to the Discovery of New Antibacterial Drugs

The emergence of bacteria that are multiply resistant to commonly used antibiotics has created the medical need for novel classes of antibacterial agents. The unique challenges to the discovery of new antibacterial drugs include the following: spectrum, selectivity, low emergence of ...

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Mouse Models of Type II Diabetes Mellitus in Drug Discovery

Type II diabetes is a fast-growing epidemic in industrialized countries. Many recent advances have led to the discovery and marketing of efficient novel therapeutic medications. Yet, because of side effects of these medications and the variability in individual patient responsive ...

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Bridging Mice to Men: Using HLA Transgenic Mice to Enhance the Future Prediction and Prevention of Autoimmune Type 1 Diabetes in Humans

Similar to the vast majority of cases in humans, the development of type 1 diabetes (T1D) in the NOD mouse model is due to T-cell mediated autoimmune destruction of insulin-producing pancreatic β cells. Particular major histocompatibility complex (MHC) haplotypes (designated HLA in huma ...

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Development of Novel Major Histocompatibility Complex Class I and Class II-Deficient NOD-SCID IL2R Gamma Chain Knockout Mice for Modeling Human Xenoge

Immunodeficient mice have been used as recipients of human peripheral blood mononuclear cells (PBMC) for in vivo analyses of human xeno-graft-versus-host disease (GVHD). This xeno-GVHD model system in many ways mimics the human disease. The model system is established by intravenous or i ...

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Human FcRn Transgenic Mice for Pharmacokinetic Evaluation of Therapeutic Antibodies

Therapeutic monoclonal antibodies are widely recognized to be a most promising means to treat an increasing number of human diseases, including cancers and autoimmunity. To a large extent, the efficacy of monoclonal antibody treatment is because IgG antibodies have greatly extended ...

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Profiling of Drug Action Using Reporter Mice and Molecular Imaging

Reporter mice associated to molecular imaging represent a major asset for the study of the spatio-temporal effects of drugs in living animals. The field is still relatively young and so far the number of animals genetically modified to express a given reporter gene ubiquitously and under the co ...

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Engineering the Mouse Genome to Model Human Disease for Drug Discovery

Genetically engineered mice (GEM) have become invaluable tools for human disease modeling and drug development. Completion of the mouse genome sequence in combination with transgenesis and gene targeting in embryonal stem cells have opened up unprecedented opportunities. Adv ...

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Genetically Engineered Mouse Models in Drug Discovery Research

Genetically modified mouse models have been proven to be a powerful tool in drug discovery. The ability to genetically modify the mouse genome by removing or replacing a specific gene has enhanced our ability to identify and validate target genes of interest. In addition, many human diseases can ...

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The Sophisticated Mouse: Protecting a Precious Reagent

Definable, genetically and environmentally, the humble mouse has become a reagent with which to probe the human condition. The information thus gained is leading to a greater understanding of inter-individual variation in drug responses and disease processes and is forming the basis for ...

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Murine Model of Polymicrobial Septic Peritonitis Using Cecal Ligation and Puncture (CLP)

Although a number of animal models such as endotoxic shock and bacteremia have been used to study the pathogenesis of sepsis, cecal ligation and puncture (CLP) represents a peritonitis model with clinical features of polymicrobial infection comparable with those of peritonitis in huma ...

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Murine Model of Pneumococcal Pneumonia

Respiratory tract infections remain among the most common clinical problems worldwide. Pneumonia or inflammation of the lungs can be caused by infection with bacteria, viruses, and other organisms. Pneumonia management has been challenged by the widespread distribution of antib ...

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Murine Model of Cutaneous Infection with Streptococcus pyogenes

Despite the medical advances achieved during the last century to fight against bacteria, viruses, fungi and parasites, infectious diseases are still a major cause of death, disability, and social and economic upheaval for millions around the world. Challenges remain in countering micr ...

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Neuromuscular Disease Models and Analysis

Neuromuscular diseases can affect the survival of peripheral neurons, their axons extending to peripheral targets, their synaptic connections onto those targets, or the targets themselves. Examples include motor neuron diseases such as amyotrophic lateral sclerosis, perip ...

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Improving Toxicity Screening and Drug Development by Using Genetically Defined Strains

According to the US Food and Drugs Administration (Food and Drug Administration (2004) Challenge and opportunity on the critical path to new medical products.) “The inability to better assess and predict product safety leads to failures during clinical development and, occasionally, ...

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Mouse Models of Neurodegenerative Diseases: Criteria and General Methodology

The major symptom of Alzheimer’s disease is rapidly progressing dementia, coinciding with the formation of amyloid and tau deposits in the central nervous system, and neuronal death. At present familial cases of dementias provide the most promising foundation for modelling neurodeg ...

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Experimental Models of Anxiety for Drug Discovery and Brain Research

Animal models have been vital to recent advances in experimental neuroscience, including the modeling of common human brain disorders such as anxiety, depression, and schizophrenia. As mice express robust anxiety-like behaviors when exposed to stressors (e.g., novelty, bright lig ...

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Virus-Delivered RNA Interference in Mouse Brain to Study Addiction-Related Behaviors

The use of viral vectors for gene transfer to specific brain regions is a powerful tool for determining gene function in mouse behavioral models. We have employed a lentiviral vector to deliver small-hairpin RNAs to areas of mouse brain implicated in behaviors relevant to drug addiction, such as ...

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Mouse Models for Studying Depression-Like States and Antidepressant Drugs

Depression is a common psychiatric disorder, with diverse symptoms and high comorbidity with other brain dysfunctions. Due to this complexity, little is known about the neural and genetic mechanisms involved in depression pathogenesis. In a large proportion of patients, current ant ...

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