In the process of preclinical development, a compound or biological agent must go through the testing phases, for the following targets, which are the identification of potential targets of disease treatment and screening out the potential candidates that must go through toxicity test before clinical tests.

What is the basis of preclinical testing?
According to FDA regulations, a series of tests are required before a new drug is approved for marketing. In the first stage, basic research identifies a hypothetical target for the treatment of a certain disease, and then small molecules or biological compounds are screened to discover any substances with the potential to treat the disease.

Then, a preclinical research phase follows, before which, as described above, the potential toxicity of the compound was determined. Factors such as dosage, dosing method, and dosing frequency are also studied to support the next phase of clinical trials when the compound will be tested in humans to see if it can be used to treat the disease that triggered the research.

Potential target identification
Target Identification and Validation ( is the first and foremost procedure of preclinical testing. The latest technological advancements have increased the number of potential targets. Bioinformatics tools can now be used to explore the available data to search for these potential targets, which may come from published studies or patents, gene expression and proteomics data sets, data on transgenic phenotypes, and analysis data of compounds.

Targets include a wide range of biomolecules, such as proteins, RNA, and DNA. A key requirement for taking biomolecules as targets is whether they are absorbable by the body, which means that the compound to be tested should be able to approach the target and then induce a measurable response.

Certain classes of target compounds are more suitable for different types. For example, G protein-coupled receptors are good potential targets for small molecules, and antibodies are more suitable for blocking protein-protein interactions.

How to find the "target"?
Once the treatment goal is determined, the next stage of preclinical testing will be hit identification, when different measurements need to be applied.

In high-throughput screening, a large number of compounds are tested against target compounds to see if any show the potential to enter the next stage. These rely on automated systems that can test extensive compounds without making any assumptions about how these compounds might interact with the target. In contrast, centralized screening can only detect a smaller number of compounds that are more likely to interact with the target. Other screening methods used in this stage include fragment screening (to determine the structure of the compound-target interaction protein) and physiological screening (only tissues are used instead of targets or cells).

Once determined, the target will be further studied to make the compound more selective and effective. This stage of preclinical testing studies the structure-activity relationship between the compound and the target, and then studies whether the compound interacts with the target of different species, to see whether the compound can be tested in animal disease models, an important part of toxicity testing. The compound is then refined to maintain the beneficial properties while reducing or eliminating the unfavorable aspects.

What other factors should be considered for pre-clinical testing?
The nature of the disease and the demographic characteristics of the patients are additional factors to be considered.

For example, neurodegenerative diseases (such as Alzheimer's disease) are progressive diseases and therefore require long-term treatment, which means that in preclinical testing, it is crucial to test the compound in a way that mimics long-term treatment to highlight any compounds that may cause toxicity after prolonged exposure.

The route and frequency of administration are also the factors that need to be considered in patient demographics. For example, in neurodegenerative diseases, patients will benefit more from manageable treatments, such as small tablets or liquids taken once a day or less. Focusing on compounds that can be administered in this way may become the focus of preclinical testing.

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