Category : DrugDiscoverySeries

Written on Aug, 26, 2020 by in , ,

“Fluidics” is the information extracted from bodily fluids and the understanding of liquids or fluids using small diameter volumes. Hippocrates (400 BC), Galen (200 AD) and Theophilus (700 AD) were interested in analyzing urine samples — to understand the human body and its functions (1). They compared and analyzed urine color, corresponding to patients’ symptoms. About 1000 years later, scientists worked on the behavior of fluids using glass containers with small volume and diameters.

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Written on Jan, 16, 2019 by in ,

Welcome back to the drug discovery series! In this post, we journey through target validation and assay development and validation for compound screening!

Target Validation

As mentioned earlier in the series, most small molecule drugs function by modulating the activity of their particular target protein(s). Targets may be identified in a number of ways, for example, through studying disease pathophysiology to find disease-relevant pathways, or using genome and transcriptome analysis to identify proteins that are differentially expressed and/or aberrantly translated during disease. The early stages of any drug discovery effort must include extensive target validation, ideally through a broad combination of in vitro and in vivo (animal models), cellular and ‘omics’ approaches (1).

Compound Screening  – Assay Design and Optimization

Compound screening is often carried out on a large scale, where millions of library compounds are screened. Screening on this scale is known as high throughput screening (HTS). If less than millions of compounds are deployed, one should consider low-to-medium throughput or collections of compounds. During screening, compounds are assayed for interactions with the target, typically in 96-, 384-, or 1536-well format. The nature of the interaction that is assayed between a compound and the target may be inhibition, activation, modulating, or binding.

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Written on Oct, 22, 2018 by in ,

Genetically Encoded Biosensors for Research and Drug Discovery

Mitochondrial integrity and function are pivotal to cellular energy production, and mitochondrial dysfunction has been shown to alter the cell cycle, metabolism, cell viability, gene regulation, and other critical aspects of cellular growth and survival.

Mitochondrial Dysfunction – Disease and Cytotoxicity

Mitochondrial dysfunction is associated with a broad spectrum of diseases. For example, in cancer, glycolysis persists to continuously supply ATP for tumor growth while bypassing the need for healthy mitochondria in a phenomenon known as the Warburg Effect (1). Although the underlying genetic reasons for the links between aerobic glycolysis, tumor growth, and hypoxia are not fully understood, the available evidence supports a link between the ability of cancer cells to bypass normal cellular metabolic pathways and mitochondrial dysfunction. Elsewhere, research into neurodegenerative disorders (e.g., Alzheimer’s, amyotrophic lateral sclerosis (ALS), Huntington’s, and Parkinson’s) has revealed the essentiality of mitochondria for neuronal survival, cellular metabolism, and reactive oxygen species production (ROS). Neurons depend on oxidative phosphorylation as a critical source of energy and are very sensitive to intracellular ROS. Consequently, mitochondrial biogenesis and dysfunction are associated with neurodegeneration and aging.

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