zebrafish drug discovery

2020 Nov 19;11:599244. doi: 10.3389/fphys.2020.599244. Batista-Filho J, Falcão MAP, Maleski ALA, Soares ABS, Balan-Lima L, Disner GR, Lima C, Lopes-Ferreira M. Toxicol Rep. 2020 Dec 10;8:13-22. doi: 10.1016/j.toxrep.2020.12.004. Then, they translated the results obtained from the PK model to humans and … This consistency suggested the zebrafish assay would be rigorous enough to serve as a platform for phenotypic drug discovery. Zebrafish larvae have evolved into a very attractive model for drug discovery. 2010 Nov-Dec;3(11-12):689-92. doi: 10.1242/dmm.006312. Toxicol Sci 102(S-1):407, #1977 Google Scholar Hill AJ, Teraoka H, Heideman W, Peterson RE (2005) Zebrafish as a … 4, No. Rubel and Raible then teamed up with Julian Simon, a molecular pharmacologist at Fred Hutchinson Cancer Research Center.  |  For the zebrafish to become useful in drug development more broadly, key hurdles must be overcome, including a more comprehensive elucidation of the similarities and differences between human and zebrafish biology. 1 January 2005 | Nature Reviews Drug Discovery, Vol. This teleost shares several inflammatory mediators and receptors with mammals. -. In the past two decades, our understanding of disease biology and drug toxicity has grown significantly owing to thousands of studies on this tiny vertebrate. Unpredicted human safety events in clinical trials for new drugs are costly in terms of human health and money. eCollection 2021. More recently, the use of zebrafish as a model of human brain diseases and for drug discovery has increased (2, 173). (12)Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Zebrafish Facility - Drug Discovery and Development Based on Quantitative Systems Pharmacology (QSP) eCollection 2020. Recently, we have isolated the rat (r) H + /organic cation antiporter multidrug and toxin extrusion 1 (MATE1) and reported its tissue distribution and transport characteristics. Abstract:The zebrafish is fast becoming a leading and prominent model organism used by researchers for developmental biology, and research in modeling human diseases in zebrafish is being undertaken at a fast pace. Inflammatory disease modeling in either larvae or adult zebrafish represents a promising tool for the screening of new anti-inflammatory compounds, contributing to our understanding of the mechanisms involved in chronic inflammatory conditions. Journal Proceedings of the National Academy of Sciences. Here, we summarize recent work on drug discovery and toxicity in zebrafish embryos.  |  The expanding availability of zebrafish models for different MDs now makes this approach a realistic option for identifying novel downstream therapeutics for many of … Cytochrome P450 Expression and Chemical Metabolic Activity before Full Liver Development in Zebrafish. Zebrafish is being used in Roche research and early development for both safety and efficacy studies. Turning off the green. Carla Bonan has recognized expertise in zebrafish research, with a special focus on the purinergic system and disease modeling. Recent studies have begun to establish the capabilities and limitations of zebrafish for disease modelling, drug screening, target identification, pharmacology, and toxicology. Maria Campos has been working on inflammatory pathways and animal models of inflammation for almost 20 years. Toxicol Sci 102(S-1):407, #1977 Google Scholar Hill AJ, Teraoka H, Heideman W, Peterson RE (2005) Zebrafish as a … Christensen C, Þorsteinsson H, Maier VH, Karlsson KÆ. Multi-parameter Behavioral Phenotyping of the MPP+ Model of Parkinson's Disease in Zebrafish. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Epub 2010 Sep 27. 2 Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 209 Victoria Street, Toronto, ON, CA. Zebrafish have been extensively used in the study of the CNS. First, all studies used zebrafish during embryonic, larval or … Accepted: 01/09/2014 Abstract The zebrafish ( Danio rerio) has become a widely used vertebrate model organism for drug discovery because of its hi gh fecundity, transparent embryos and larvae, morphological and p hysiological similarity to mammals, allowing in vivo analysis of embryogenesis and organogenesis combined with ease of use and low cost. Zebrafish Xenografts for Drug Discovery and Personalized Medicine Trends Cancer. In vivo drug discovery in the zebrafish. © 2020 Elsevier Ltd. All rights reserved. 1. More On: drug discovery, Duchenne muscular dystrophy, image-based screening, iPS cells, Leonard Zon, muscle disease, Regenerative medicine, stem cells, zebrafish In a one-two-three punch, a rapid screen in zebrafish can quickly identify a short list of drug candidates to test in mice and in patient-derived cells. Epub 2020 Apr 17. Potential approaches to overcoming the hurdles to drug discovery in the face of complex biology including in vivoscreening of zebrafish genetic disease models. 2012;52:433-53. doi: 10.1146/annurev-pharmtox-010611-134751. The zebrafish is an important and widely used vertebrate model organism in scientific research, for example in drug development, in particular pre-clinical development. Despite more than 30 phase II clinical trials since 1985, there is no standard chemotherapy or drug regimen for ACC. Zebrafish Services. But here in a Cincinnati Children's laboratory, the freshwater variant plays a vital role in scientific discovery. -, Nat Chem Biol. We are excited to be the exclusive commercial partner in Denmark, Sweden, Norway, Finland and Poland for the innovative and successful CRO company, ZeClinics - specialised in usingzebrafish for Drug Discovery and BioMedical Research. https://doi.org/10.1016/j.drudis.2020.09.036. Students will search human disease databases to identify diseases that could be modeled in zebrafish. Drug absorption and drug metabolism in the zebrafish Whether findings from drug discovery screens derived from Zebrafish larvae have evolved into a very attractive model for drug discovery. Zebrafish is a small teleost (bony) fish used in many areas of pharmacology and toxicology. -, Cell Rep. 2013 Sep 12;4(5):898-904 In retrospect, many advantages can be named, but pitfalls must also be highlighted. Recently, zebrafish larvae were used for detecting retinal toxicity in pharmaceutical pipeline discovery compounds, replacing studies in mammalian models and demonstrating clear value from zebrafish for drug discovery toxicology (Figure 5). Epub 2011 Oct 19. The use of zebrafish model in prostate cancer therapeutic development and discovery. The creation of mutant strains reinforces zebrafish use in inflammation research. Participants chronicled their use of zebrafish to assess drug toxicity and efficacy, to find bioactive small molecules, and even to find genes coding for potential new drug targets. Overall, these models exhibit conserved biochemical and neurobehavioral features. (11)Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Department of Medicine and Physiology, University of Toronto, 209 Victoria Street, LKSKI Rm 519, Toronto, ON, M5B 1T8, Canada. 2011;105:493-516. doi: 10.1016/B978-0-12-381320-6.00021-7. 3 Department of Physiology, University of Toronto, Toronto, ON, CA. 2021 Jan 3. doi: 10.1007/s00280-020-04211-z. Zebrafish represent one of the few vertebrate models currently amenable to a phenotype-based drug discovery strategy [ 12 ]. This animal model has advantages for the discovery of anti-inflammatory drugs, such as the potential for real-time assessment of cell migration mechanisms. Among different classes of psychotropic drugs, hallucinogenic agents exert one of the most prominent effects on human and animal behaviors, markedly altering sensory, motor, affective, and cognitive responses. Multiple studies have validated the zebrafish xenograft assay using patient-derived cells from other ex vivo models, thus extending the usefulness of these platforms [ It is also notable for its regenerative abilities, and has been modified by researchers to produce many transgenic strains. This consistency suggested the zebrafish assay would be rigorous enough to serve as a platform for phenotypic drug discovery. Zebrafish also offer the possibility of an assay to study blood coagulation at an earlier stage of the drug discovery process than that at which the … Zebrafish xenografts are proven models of human cancer biology that provide rapid in vivo validation of anticancer drugs and drug targets. Advantages of the zebrafish embryo as a model. Cancer Chemother Pharmacol. Abstract. Annu Rev Pharmacol Toxicol. -, Nat Commun. 2020 Jul;6(7):569-579. doi: 10.1016/j.trecan.2020.03.012. The use of zebrafish in pharmaceutical research and discovery and drug development is mainly screening of lead compounds, target identification, target validation, morpholino oligonucleotide screens, assay development for drug discovery, physiology based drug discovery, quantitative structure-activity relationship (QSAR) and structure – activity relationships (SAR) study and drug toxicity study. Indeed, various sequencing projects in typical and refractory epilepsy are starting to shed insight into the complex genetics underlying this disorder. 2011;105:525-41. doi: 10.1016/B978-0-12-381320-6.00023-0. Zebrafish, Drug discovery; Get e-Alerts. Overall, these models exhibit conserved biochemical and neurobehavioral features. Pharmacology and toxicology of pahayokolide A, a bioactive metabolite from a freshwater species of isolated from the Florida Everglades. Zebrafish is a small teleost (bony) fish used in many areas of pharmacology and toxicology. Zebrafish embryos are permeable to drugs and can easily be manipulated using well‐established genetic and molecular approaches. Recently published methods facilitate genetical engineering of zebrafish, allowing the study of targets of interest in an easily accessible vertebrate system: a multiorgan culture model. Here, we review several zebrafish models of movement disorders and discuss their translational value. It has been widely recognized that zebrafish can be powerful tools in the drug discovery field, given advantages such as high fecundity, ease of drug administration, similarity to mammals in terms of structures and functions of various tissues, and suitability … This feature has two main advantages, it saves time in the procedure if compared, for example, with the time invested in injecting drugs in mice. That’s because sponsors choose CROs not on the basis of location but on the basis of expertise in related drug development, specific technological prowess, or experience with specific disease states. This is an advantage of the model that allows for high‐throughput phenotypic screening, especially if transgenic lines are used 74 . The real-time evaluation of cell migration is an advantage of zebrafish. 2020 Dec 11;13(12):456. doi: 10.3390/ph13120456. COVID-19 is an emerging, rapidly evolving situation. Adult zebrafish xenografts are similar to mouse xenografts but … Here, we review several zebrafish models of movement disorders and discuss their translational value. Modeling Inherited Cardiomyopathies in Adult Zebrafish for Precision Medicine. The zebrafish has become a prominent vertebrate model for disease and has already contributed to several examples of successful phenotype-based drug discovery. 2.1. In order to answer these questions, the Division of Analytical Biosciences the Division of Pharmacology in the Leiden Academic Centre for Drug Research and the Institute of Biology Leiden joined efforts to develop the first pharmacokinetics (PK) model in zebrafish larvae by using paracetamol as paradigm drug 2. It has been widely recognized that zebrafish can be powerful tools in the drug discovery field, given advantages such as high fecundity, ease of drug administration, similarity to mammals in terms of structures and functions of various tissues, and suitability … But here in a Cincinnati Children's laboratory, the freshwater variant plays a vital role in scientific discovery. Zebrafish represent one of the few vertebrate models currently amenable to a phenotype-based drug discovery strategy [ 12 ]. Additionally, zebrafish display a repertoire of inflammatory cells, mediators, and receptors that are similar to those in mammals, including humans. This model is powerful in its breadth of application and tractability for research. Hill AJ (2008b) Zebrafish use in drug discovery. By continuing you agree to the use of cookies. Drug Discovery Zebrafish provide a unique opportunity for phenotypic drug discovery and development. (Philadelphia, PA) -Researchers at the University of Pennsylvania School of Medicine have discovered that zebrafish produce enzymes analogous to the two human cyclooxygenase (COX) enzymes - COX-1 and -2 - proteins that have a role in a variety of ailments including cardiovascular disease, some types of cancer, and arthritis. Drug Discovery Zebrafish provide a unique opportunity for phenotypic drug discovery and development. In retrospect, many advantages can be named, but pitfalls must also be highlighted. Zebrafish, Drug discovery; Get e-Alerts. Abstract. Among all the models available in drug discovery, we decided to focus on zebrafish due to reducing animal use in preclinical assays is important for you. Copyright © 2021 Elsevier B.V. or its licensors or contributors. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Zebrafish as a model for inflammation and drug discovery. 1 Zebrafish Centre for Advanced Drug Discovery, St. Michael's Hospital, 209 Victoria St, Toronto, Ontario, Canada M5B 1T8. As our understanding increases and as the technologies for manipulating zebrafish improve, it is hoped that the zebrafish will have a key role in accelerating the emergence of precision medicine. But here in a Cincinnati Children’s laboratory, the freshwater variant plays a vital role in scientific discovery. Online ahead of print. Because of all the previously described advantages that the zebrafish animal model presents, it has recently stood out in the drug discovery process (i) to identify molecules that specifically ameliorate a disease phenotype and (ii) to perform detailed characterization studies around optimized compounds, focusing not only on efficacy (dose-response) but also on toxicity and/or mechanism. Would you like email updates of new search results? The zebrafish (Danio rerio) is a vertebrate with many attractive characteristics for use in drug discovery, such as a small size, transparency, gene and protein similarity with mammals (80% or more), and ease of genetic modification to establish human disease models. Popular in aquariums all over the world, the zebrafish is native to South Asia. wenx@smh.ca. It permits the screening of compound libraries in a whole organism. The zebrafish has emerged as a powerful vertebrate model for studying liver‐associated disorders. The zebrafish has become a prominent vertebrate model for disease and has already contributed to several examples of successful phenotype-based drug discovery. Dis Model Mech. Please enable it to take advantage of the complete set of features! Zebrafish have emerged as unsurpassed models for imaging tumor metastasis. DRUG DISCOVERY & DEVELOPMENT IS GLOBAL The zebrafish CRO community is collaborative and international in reach. Zebrafish, long a useful proxy for humans in drug development, just got an upgrade courtesy of BioTek’s Lionheart FX automated microscope and Gen5 microplate reader. Methods Cell Biol. The session demonstrated the utility of zebrafish in a wide range of applications in drug discovery. Epilepsy is a heterogenous disease, with both genetic and environmental factors contributing to its aetiology. ZeTox SERVICE Full toxicology screening to obtain high quality data in a fast and cost-effective manner. Zebrafish have been extensively used in the study of the CNS. In this review, we provide an overview of the characterization of inflammatory responses in zebrafish, emphasizing its relevance for drug discovery in this research area. Recently published methods facilitate genetical engineering of zebrafish, allowing the study of targets of interest in an easily accessible vertebrate system: a multiorgan culture model. Popular in aquariums all over the world, the zebrafish is native to South Asia. Front Behav Neurosci. Zebrafish Facility The University of Pittsburgh School of Medicine’s aquatics research facility is one of the largest in the world. Take home message In vivo screening in faithful disease models allows the effects of drugs on integrative physiology and disease biology to be captured during the screening process, in a manner agnostic to potential drug target or targets. The extensive use of zebrafish xenografts for mechanistic and drug discovery experiments lends support to the idea that this platform will be useful for testing the drug sensitivity of patient cells. wenx@smh.ca. The expanding availability of zebrafish models for different MDs now makes this approach a realistic option for identifying novel downstream therapeutics for many of … HHS Bringing a new drug to the market costs an average of US$2.6 billion and takes more than 10 years from discovery to regulatory approval. Liver damage is a crucial problem in the process of drug development and zebrafish have proven to be an important tool for the high‐throughput screening of drugs for hepatotoxicity. Zebrafish: drug discovery and Personalized Medicine Trends Cancer 12 ] safety events in clinical trials for drugs. Be highlighted minimize those events with diligent preclinical safety testing platform for phenotypic drug industry. 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