In Vivo Models for Drug Discovery

2014 ◽  
Keyword(s):  
Drug Discovery ◽  
In Vivo Models

scholarly journals A reliable and affordable 3D tumor spheroid model for natural product drug discovery: A case study of curcumin

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Loh Teng Hern Tan ◽  
Liang Ee Low ◽  
Siah Ying Tang ◽  
Wei Hsum Yap ◽  
Lay Hong Chuah ◽  
...  
Keyword(s):  
Cell Culture ◽  
Drug Discovery ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Automated Image Analysis ◽  
Tumor Spheroids ◽  
Culture Methods ◽  
In Vivo Models

Three-dimensional cell culture methods revolutionize the field of anticancer drug discovery, forming an important link-bridge between conventional in vitro and in vivo models and conferring significant clinical and biological relevant data. The current work presents an affordable yet reproducible method of generating homogenous 3D tumor spheroids. Also, a new open source software is adapted to perform an automated image analysis of 3D tumor spheroids and subsequently generate a list of morphological parameters of which could be utilized to determine the response of these spheroids toward treatments. Our data showed that this work could serve as a reliable 3D cell culture platform for preclinical cytotoxicity testing of natural products prior to the expensive and time-consuming animal models

Imaging Microphysiological Systems: A Review

2020 ◽  
Author(s):  
Samantha Peel ◽  
Mark Jackman
Keyword(s):  
Drug Discovery ◽  
Animal Studies ◽  
Imaging Techniques ◽  
Quantitative Information ◽  
In Vitro Models ◽  
Microscopy Imaging ◽  
In Vivo Models ◽  
Microphysiological Systems

Microphysiological Systems (MPS), often referred to as 'organ-on-chips' are microfluidic-based in vitro models that aim to recapitulate the dynamic chemical and mechanical microenvironment of living organs. MPS promise to bridge the gap between in vitro and in vivo models, and ultimately improve the translation from pre-clinical animal studies to clinical trials. However, despite the explosion of interest in recent years, and the obvious rewards for such models which could improve R&D efficiency and reduce drug attrition in the clinic, the pharmaceutical industry has been slow to fully adopt this technology. The ability to extract robust, quantitative information from MPS at scale is a key requirement if these models are to impact drug discovery and the subsequent drug development process. Microscopy imaging remains a core technology that enables the capture of information at the single cell level and with subcellular resolution. Furthermore, such imaging techniques can be automated, increasing throughput, enabling compound screening. In this review we discuss a range of imaging techniques that have been applied to MPS of varying focus, such as organoids and organ-chip-type models. We outline the opportunities these technologies can bring in terms of understanding mechanistic biology, but also how they could be used in higher-throughput screens, widening the scope of their impact in drug discovery. We discuss the associated challenges of imaging these complex models and the steps required to enable full exploitation. Finally, we discuss the requirements for MPS, if they are to be applied at a scale necessary to support drug discovery projects.

scholarly journals Using Zebrafish as a Disease Model to Study Fibrotic Disease

2021 ◽  
Vol 22 (12) ◽  
pp. 6404
Author(s):  
Xixin Wang ◽  
Daniëlle Copmans ◽  
Peter A. M. de Witte
Keyword(s):  
Liver Disease ◽  
Drug Discovery ◽  
Animal Models ◽  
Disease Model ◽  
New Drugs ◽  
Disease Models ◽  
Fibrotic Disease ◽  
Comprehensive Overview ◽  
In Vivo Models

In drug discovery, often animal models are used that mimic human diseases as closely as possible. These animal models can be used to address various scientific questions, such as testing and evaluation of new drugs, as well as understanding the pathogenesis of diseases. Currently, the most commonly used animal models in the field of fibrosis are rodents. Unfortunately, rodent models of fibrotic disease are costly and time-consuming to generate. In addition, present models are not very suitable for screening large compounds libraries. To overcome these limitations, there is a need for new in vivo models. Zebrafish has become an attractive animal model for preclinical studies. An expanding number of zebrafish models of human disease have been documented, for both acute and chronic diseases. A deeper understanding of the occurrence of fibrosis in zebrafish will contribute to the development of new and potentially improved animal models for drug discovery. These zebrafish models of fibrotic disease include, among others, cardiovascular disease models, liver disease models (categorized into Alcoholic Liver Diseases (ALD) and Non-Alcoholic Liver Disease (NALD)), and chronic pancreatitis models. In this review, we give a comprehensive overview of the usage of zebrafish models in fibrotic disease studies, highlighting their potential for high-throughput drug discovery and current technical challenges.

Abstract B37: RNAi and CRISPR/Cas9-based in vivo models for drug discovery

2018 ◽  
Author(s):  
Prem K. Premsrirut ◽  
Chia-Lin Wang ◽  
Yu-ting Yang ◽  
Rafii Pelossof ◽  
Christina Leslie ◽  
...  
Keyword(s):  
Drug Discovery ◽  
In Vivo Models

RNAi and CRISPR/Cas9 based in vivo models for drug discovery

2016 ◽  
Vol 61 ◽  
pp. S208
Author(s):  
P. Premsrirut ◽  
G. Martin ◽  
L. Dow ◽  
S.Y. Kim ◽  
J. Zuber ◽  
...  
Keyword(s):  
Drug Discovery ◽  
In Vivo Models

scholarly journals Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections

2019 ◽  
Vol 4 (3) ◽  
pp. 108 ◽  
Author(s):  
Malina A. Bakowski ◽  
Case W. McNamara
Keyword(s):  
Drug Discovery ◽  
High Throughput Screening ◽  
High Speed ◽  
Intracellular Bacteria ◽  
Proof Of Concept ◽  
In Vivo Models ◽  
Filarial Worm ◽  
Long Duration ◽  
Screening Approaches

The intracellular bacteria now known as Wolbachia were first described in filarial worms in the 1970s, but the idea of Wolbachia being used as a macrofilaricidal target did not gain wide attention until the early 2000s, with research in filariae suggesting the requirement of worms for the endosymbiont. This new-found interest prompted the eventual organization of the Anti-Wolbachia Consortium (A-WOL) at the Liverpool School of Tropical Medicine, who, among others have been active in the field of antiwolbachial drug discovery to treat filarial infections. Clinical proof of concept studies using doxycycline demonstrated the utility of the antiwolbachial therapy, but efficacious treatments were of long duration and not safe for all infected. With the advance of robotics, automation, and high-speed computing, the search for superior antiwolbachials shifted away from smaller studies with a select number of antibiotics to high-throughput screening approaches, centered largely around cell-based phenotypic screens due to the rather limited knowledge about, and tools available to manipulate, this bacterium. A concomitant effort was put towards developing validation approaches and in vivo models supporting drug discovery efforts. In this review, we summarize the strategies behind and outcomes of recent large phenotypic screens published within the last 5 years, hit compound validation approaches and promising candidates with profiles superior to doxycycline, including ones positioned to advance into clinical trials for treatment of filarial worm infections.

scholarly journals Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 641
Author(s):  
Elisa Rampacci ◽  
Valentina Stefanetti ◽  
Fabrizio Passamonti ◽  
Marcela Henao-Tamayo
Keyword(s):  
Drug Discovery ◽  
Vaccine Development ◽  
Nontuberculous Mycobacteria ◽  
Critical Role ◽  
Developed Countries ◽  
Alternative Methods ◽  
In Vivo Models ◽  
Early Drug

Nontuberculous mycobacteria (NTM) represent an increasingly prevalent etiology of soft tissue infections in animals and humans. NTM are widely distributed in the environment and while, for the most part, they behave as saprophytic organisms, in certain situations, they can be pathogenic, so much so that the incidence of NTM infections has surpassed that of Mycobacterium tuberculosis in developed countries. As a result, a growing body of the literature has focused attention on the critical role that drug susceptibility tests and infection models play in the design of appropriate therapeutic strategies against NTM diseases. This paper is an overview of the in vitro and in vivo models of NTM infection employed in the preclinical phase for early drug discovery and vaccine development. It summarizes alternative methods, not fully explored, for the characterization of anti-mycobacterial compounds.

scholarly journals 3D Cell-Based Assays for Drug Screens: Challenges in Imaging, Image Analysis, and High-Content Analysis

2019 ◽  
Vol 24 (6) ◽  
pp. 615-627 ◽  
Author(s):  
Tijmen H. Booij ◽  
Leo S. Price ◽  
Erik H. J. Danen
Keyword(s):  
Content Analysis ◽  
Drug Discovery ◽  
High Throughput Screening ◽  
3D Cell Culture ◽  
Automated Analysis ◽  
In Vivo Models ◽  
Current Switch ◽  
High Content Analysis

The introduction of more relevant cell models in early preclinical drug discovery, combined with high-content imaging and automated analysis, is expected to increase the quality of compounds progressing to preclinical stages in the drug development pipeline. In this review we discuss the current switch to more relevant 3D cell culture models and associated challenges for high-throughput screening and high-content analysis. We propose that overcoming these challenges will enable front-loading the drug discovery pipeline with better biology, extracting the most from that biology, and, in general, improving translation between in vitro and in vivo models. This is expected to reduce the proportion of compounds that fail in vivo testing due to a lack of efficacy or to toxicity.

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