Preclinical Research Overview - target selection and validation Flashcards
What is the primary goal of preclinical research?
The primary goal of preclinical research is to collect data regarding drug safety, efficacy, dosing, and other factors to determine whether a drug is ready for testing in humans.
What are drug targets, and what types of molecules are most commonly targeted?
Drug targets are molecules that bind to produce a desirable therapeutic effect, with most drug targets being proteins. Increasingly, direct actions on DNA or RNA are also being considered.
How can new drug targets be identified?
New drug targets can be identified by comparing gene or protein expression levels between normal and diseased cells through pathway analysis and phenotype studies.
What role does bioinformatics play in preclinical research?
Bioinformatics is used to store, retrieve, and analyse large amounts of biological data, helping to identify disease-specific signatures by comparing DNA sequences of normal and diseased cells.
What factors do pharmaceutical companies consider when selecting diseases to target?
Pharmaceutical companies often focus on diseases prevalent in developed nations, considering both economic factors and potential medical benefits due to the significant investment required for drug research and development.
What are some sources of compounds for drug discovery?
Compounds can be sourced from the plant kingdom, microbial world (like fungi and bacteria), marine organisms (such as sponges and fish), animal venoms and toxins, and synthetic compounds created in laboratories.
What is high throughput screening (HTS), and why is it important?
High throughput screening (HTS) is an automated method used to rapidly test thousands to millions of samples for biological activity, which helps identify potential drug candidates efficiently.
What is the difference between in vitro, in vivo, and ex vivo experiments?
In vitro experiments are conducted outside an organism (e.g., in test tubes), in vivo experiments are performed within a living organism, and ex vivo experiments involve studying intact tissues or organs outside a living organism.
What are some limitations of using cell lines in preclinical research?
Cell lines, while useful for studying various cellular processes, may not accurately reflect the complex biology of living organisms, and their behaviour can differ significantly from that of cells in a whole organism.
What are some challenges associated with animal models in preclinical research?
Animal models may not fully replicate human diseases, have limited genetic diversity, and their lifespan is relatively short compared to the long-term progression of human diseases. Additionally, environmental conditions in animal studies can differ from human conditions.
What is the purpose of a primary screen in drug discovery?
The primary screen is used to identify active compounds from a compound library that interact with the drug target. It typically involves high throughput screening to test a large number of potential candidates efficiently.
How many compounds are typically validated in a secondary screen?
In a secondary screen, the validation process typically focuses on 1,000 to 20,000 compounds that were identified as active in the primary screen, allowing for a more detailed assessment of their efficacy and selectivity.
What is the significance of selectivity in drug development?
Selectivity refers to a drug’s ability to target specific proteins or pathways while minimizing effects on similar proteins. High selectivity can reduce side effects and improve the therapeutic profile of a drug.
What is the role of in silico experiments in preclinical research?
In silico experiments use computer simulations to model biological processes, predict interactions, and analyse data, aiding in target identification, compound screening, and optimization without the need for physical experiments.
Why is the morphology of cells important in drug target identification?
Analysing the morphology of cells can reveal structural and functional differences between normal and diseased cells, helping researchers identify potential drug targets by understanding how disease alters cellular characteristics.
