Introduction to Model Systems in Drug Discovery

2005 ◽  
pp. 1-7
Author(s):  
Kevin Fitzgerald ◽  
Pamela M. Carroll
Keyword(s):  
Drug Discovery ◽  
Model Systems

scholarly journals New hepatitis C virus drug discovery strategies and model systems

2012 ◽  
Vol 7 (9) ◽  
pp. 849-859 ◽  
Author(s):  
Snawar Hussain ◽  
Naina Barretto ◽  
Susan L Uprichard
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Discovery ◽  
Model Systems

scholarly journals hiPSC-Derived Cardiac Tissue for Disease Modeling and Drug Discovery

2020 ◽  
Vol 21 (23) ◽  
pp. 8893
Author(s):  
Junjun Li ◽  
Ying Hua ◽  
Shigeru Miyagawa ◽  
Jingbo Zhang ◽  
Lingjun Li ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Cardiac Tissue ◽  
Disease Modeling ◽  
Disease Model ◽  
Induced Pluripotent Stem Cell ◽  
Model Systems ◽  
Toxicity Screening ◽  
The Difference ◽  
Induced Pluripotent ◽  
Novel Drug

Relevant, predictive normal, or disease model systems are of vital importance for drug development. The difference between nonhuman models and humans could contribute to clinical trial failures despite ideal nonhuman results. As a potential substitute for animal models, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) provide a powerful tool for drug toxicity screening, modeling cardiovascular diseases, and drug discovery. Here, we review recent hiPSC-CM disease models and discuss the features of hiPSC-CMs, including subtype and maturation and the tissue engineering technologies for drug assessment. Updates from the international multisite collaborators/administrations for development of novel drug discovery paradigms are also summarized.

scholarly journals From bench to patient: model systems in drug discovery

2015 ◽  
Vol 8 (10) ◽  
pp. 1171-1174 ◽  
Author(s):  
Matthew D. Breyer ◽  
A. Thomas Look ◽  
Alessandra Cifra
Keyword(s):  
Drug Discovery ◽  
Model Systems ◽  
Patient Model

Model systems in drug discovery: chemical genetics meets genomics

2003 ◽  
Vol 99 (2) ◽  
pp. 183-220 ◽  
Author(s):  
Pamela M Carroll ◽  
Brian Dougherty ◽  
Petra Ross-Macdonald ◽  
Kailtin Browman ◽  
Kevin FitzGerald
Keyword(s):  
Drug Discovery ◽  
Chemical Genetics ◽  
Model Systems

scholarly journals Fibroblasts cell lines misclassified as cancer cell lines

2017 ◽  
Author(s):  
Antoine de Weck ◽  
Hans Bitter ◽  
Audrey Kauffmann
Keyword(s):  
Cancer Research ◽  
Drug Discovery ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Model Systems ◽  
Genomic Characterization

Large collections of immortalized cancer cell lines have been widely used as model systems for cancer research and drug discovery. Some of these models however display more fibroblast-like than cancer-like characteristics based on their genetic and genomic characterization. The correct annotation of these cell lines remains a challenge. Here, we report the outcome of our analysis on a large cancer cell line collection, where we found a subset of cell lines misclassified.

Prediction of brain:blood unbound concentration ratios in CNS drug discovery employing in silico and in vitro model systems

2018 ◽  
Vol 23 (7) ◽  
pp. 1357-1372 ◽  
Author(s):  
Houfu Liu ◽  
Kelly Dong ◽  
Wandong Zhang ◽  
Scott G. Summerfield ◽  
Georg C. Terstappen
Keyword(s):  
Drug Discovery ◽  
In Silico ◽  
In Vitro Model ◽  
Model Systems ◽  
Unbound Concentration ◽  
Vitro Model ◽  
Concentration Ratios

Animal Models of Mood Disorders

2013 ◽  
pp. 411-424
Author(s):  
Georgia E. Hodes ◽  
Scott J. Russo
Keyword(s):  
Drug Discovery ◽  
Animal Models ◽  
Mood Disorders ◽  
Diagnostic Criteria ◽  
Selective Breeding ◽  
Model Systems ◽  
Breeding Strategies ◽  
Biological Mechanisms ◽  
Complex Genetics ◽  
Behavioral Assays

This chapter covers practical and theoretical information concerning the validity of current animal models of mood disorders, with a focus on depression. These models range from the stress based methods used to induce depression-like responses in normal animals, to those that use the complex genetics of selective breeding strategies that predispose subsets of animals to a depression-like phenotype. The validity of each model is discussed with regard to human depression, including similarities to known changes in peripheral and neurobiological markers. The author’s suggest that by utilizing a battery of behavioral assays in model systems, it may be possible to eventually develop diagnostic criteria in humans based on valid biological mechanisms and move drug discovery efforts beyond monoamine based antidepressants

scholarly journals Conservation of the structure and function of bacterial tryptophan synthases

IUCrJ ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 649-664 ◽  
Author(s):  
Karolina Michalska ◽  
Jennifer Gale ◽  
Grazyna Joachimiak ◽  
Changsoo Chang ◽  
Catherine Hatzos-Skintges ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Legionella Pneumophila ◽  
Pathogenic Bacteria ◽  
Structural Information ◽  
Model Systems ◽  
Hydroxyl Group ◽  
Kinetic Properties ◽  
Tryptophan Synthase ◽  
Tryptophan Biosynthesis ◽  
Human Pathogens

Tryptophan biosynthesis is one of the most characterized processes in bacteria, in which the enzymes from Salmonella typhimurium and Escherichia coli serve as model systems. Tryptophan synthase (TrpAB) catalyzes the final two steps of tryptophan biosynthesis in plants, fungi and bacteria. This pyridoxal 5′-phosphate (PLP)-dependent enzyme consists of two protein chains, α (TrpA) and β (TrpB), functioning as a linear αββα heterotetrameric complex containing two TrpAB units. The reaction has a complicated, multistep mechanism resulting in the β-replacement of the hydroxyl group of L-serine with an indole moiety. Recent studies have shown that functional TrpAB is required for the survival of pathogenic bacteria in macrophages and for evading host defense. Therefore, TrpAB is a promising target for drug discovery, as its orthologs include enzymes from the important human pathogens Streptococcus pneumoniae, Legionella pneumophila and Francisella tularensis, the causative agents of pneumonia, legionnaires' disease and tularemia, respectively. However, specific biochemical and structural properties of the TrpABs from these organisms have not been investigated. To fill the important phylogenetic gaps in the understanding of TrpABs and to uncover unique features of TrpAB orthologs to spearhead future drug-discovery efforts, the TrpABs from L. pneumophila, F. tularensis and S. pneumoniae have been characterized. In addition to kinetic properties and inhibitor-sensitivity data, structural information gathered using X-ray crystallography is presented. The enzymes show remarkable structural conservation, but at the same time display local differences in both their catalytic and allosteric sites that may be responsible for the observed differences in catalysis and inhibitor binding. This functional dissimilarity may be exploited in the design of species-specific enzyme inhibitors.

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