China
Africa
Explore chapters and articles related to this topic
The Evolution of Anticancer Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
During the past three decades, various new chemical methodologies have been developed that allow large compound collections (i.e., libraries) to be produced for use in high-throughput screening operations. Compound collections are commercially available from companies specializing in this area, and are usually provided in a multi-well plate format, with an accurately known amount of each compound dispensed into each well. However, pharmaceutical companies and other research organizations may have their own compound collections synthesized in-house and built up over many years.
Evaluation Models for Drug Transport Across the Blood–Brain Barrier
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
In vitro models find a suitable role in new drug research and development process which includes various stages like target identification, hit identification, lead identification, and finally optimization of the product. The first stage involves screening numerous compounds by high throughput screening when a target is identified. Simple models like monolayer and co-culture models are mainly used in the first step. The validation of identified compound and SAR are usually carried out in optimization stage which utilizes in vitro models like static co-culture and dynamic models that are sensitive to in vivo conditions. The correlation with human cells is required to be carried out to avoid interspecies variability at various stages of development (Paradis et al., 2016).
“Kidney in a Dish” Organoids for PKD
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
Nelly M. Cruz, Benjamin S. Freedman
To bridge this gap, human kidney organoid cultures have recently emerged as a new system for studying PKD.7–11 This “kidney in a dish” organoid system has several strengths: Human cysts form from kidney tubules in a PKD-specific way.It is a flexible, defined-component system readily accessible to microscopy and experimental perturbation for extended periods of time.PKD1 and PKD2 are endogenously expressed, and can be monitored with specific antibodies, or mutated using gene-editing systems.It is amenable to automation and high-throughput screening using liquid-handling robots.
3D bioprinting for organ and organoid models and disease modeling
Published in Expert Opinion on Drug Discovery, 2023
Amanda C. Juraski, Sonali Sharma, Sydney Sparanese, Victor A. da Silva, Julie Wong, Zachary Laksman, Ryan Flannigan, Leili Rohani, Stephanie M. Willerth
A recent review on high-throughput screening assays highlighted three crucial principles for selecting targets for high-throughput screening: disease relevance, chemical tractability, and screenability [62]. Disease relevance means selecting targets that have strong links to clinical disease. However, sometimes the most valid targets may not be novel, while highly novel targets may not have a strong correlation to disease. Chemical tractability refers to the probability of finding a compound that produces the desired effect and is compatible with the screening technology. Finally, screenability is the ability to develop a high-quality screening assay that is robust and effective. These three principles provide a framework for future screening assays that use three-dimensional organoids and cell assays. With the increasing use of 3D bioprinting in drug discovery, it is crucial to select the most appropriate targets for screening. The use of 3D bioprinting offers a physiologically relevant environment that can improve drug screening accuracy. The incorporation of relevant cell types and the ability to mimic in vivo-like environments provides a valuable tool to understand drug responses and improve drug discovery.
Industrializing AI-powered drug discovery: lessons learned from the Patrimony computing platform
Published in Expert Opinion on Drug Discovery, 2022
Mickaël Guedj, Jack Swindle, Antoine Hamon, Sandra Hubert, Emiko Desvaux, Jessica Laplume, Laura Xuereb, Céline Lefebvre, Yannick Haudry, Christine Gabarroca, Audrey Aussy, Laurence Laigle, Isabelle Dupin-Roger, Philippe Moingeon
Researchers can then validate target hypotheses, through an experimental confirmation that disease activity is impacted following perturbation of the target of interest with a drug or a tool compound. Conducting wet-lab gene inhibition (e.g. via CRISPR-Cas9 deletion or RNA silencing) or preclinical experiments by using cellular assays or animal models are commonly implemented to corroborate the hypothesis that drugs interacting with the target exhibit the anticipated pharmacological activity. Once a therapeutic target has been selected, multiple processes streamlined by the pharmaceutical industry can be used to identify small molecules or biologicals interacting with it. For instance, High-Throughput Screening (HTS) can be implemented to test the company’s proprietary compound library in various molecular or cell-based assay systems in order to identify drug candidates [65]. As of today, another strategy relies upon dedicated computational methods to select in silico drugs predicted to engage the target of interest [15].
Duchenne Muscular Dystrophy: recent advances in protein biomarkers and the clinical application
Published in Expert Review of Proteomics, 2020
Being indispensable for proteomics studies, antibodies are both praised and condemned, and their performance continuously scrutinized in particular since, antibody specificity is context and application dependent [87]. Academic efforts like the The Human Protein Atlas project [83] and commercial producers ensure development and access to large numbers of antibodies, validated according to developed guidelines [88,89]. In particular, the guidelines for enhanced validation of antibodies designed by the International Working Group for Antibody Validation (IWGAV), an ad-hoc formed group of leading researchers, promotes rigorous validation of such reagents and has been adopted by researchers and leading antibody producers [89–91]. Beside antibodies development of short single-stranded oligonucleotides as affinity reagents and the SomaLogic technology enabled researchers to analyze more than 1,000 targets in cross-sectional studies in the context of DMD [92–96]. The assay relies on the capture of the target in its native conformation to immobilized protein-specific Slow Off-rate Modified DNA aptamers (SOMAmers). The SOMAmer-target complex is isolated from the sample and subsequent dissociation of the complex, the SOMAmer quantified. Quantification is achieved through hybridization of the SOMAmers to an array using the SomaScan platform. The platform has a high multiplexing capacity that allows analysis of 5,000 targets simultaneously. Although the high-throughput screening methods are useful biomarker discovery tools, confirmation of results with more targeted assays eg. ELISA is necessary.