What Is Drug Screening?

Drug screening refers to the evaluation of biological activity, pharmacological effects, and medicinal value of substances (sampling) that may be used as drugs using appropriate methods. Drug screening is screening at the biochemical and cellular levels.

Drug screening is divided into high-throughput and virtual drug screening.

Chinese name: Drug screening
Category: Screening for biochemical and cellular levels

Classification: High-throughput and virtual drug screening
Experiment: Activity test

Drug screening definition

In a broad sense: for specific requirements and purposes, through appropriate methods and technologies, the main technologies are genomics, proteomics, metabolomics, computational biology, biochip technology, microfluidic chip technology, etc. Within a selectable range, the process of drug optimization is performed. Therefore, drug screening includes prescription screening during the research of new drugs, and the drugs that meet the requirements are selected according to specific purposes.

Narrow sense: Screening refers to the use of experimental techniques. ^[1]

Drug screening activity test

Drug screening is a step in the testing and acquisition of compounds with specific physiological activity in the modern drug development process. It refers to the process of selecting compounds with high activity for a specific target by a large number of compounds or new compounds through standardized experimental methods . The process of drug screening is essentially the process of conducting pharmacological activity experiments on compounds. With the development of drug development technology, the physiological activity experiments on new compounds have gradually changed from early confirmatory experiments to screening experiments, the so-called Drug screening.

As a screening, it is necessary to make a horizontal comparison of the physiological activities of different compounds, so the experimental protocol for drug screening must be characterized by standardization and quantification. With the development of combinatorial chemistry and computational chemistry, people have the ability to synthesize and isolate multiple compounds on a large scale in a short period of time. Therefore, drug screening has gradually become one of the main ways to find lead compounds in the modern new drug development process. ^[1]

Drug screening screening model

The screening model is a pharmacological experimental model used in drug screening experiments. Because drug screening requires experimental protocols to have standardized and quantitative features, animal experiments common in traditional pharmacological experiments are less used in drug screening. Different, drug screening can be divided into biochemical level screening and cell level screening.

Biochemical-level drug screening design experiments with targets of the intended drug development. Generally speaking, the targets of this role are proteins with specific physiological functions, such as enzymes and receptors. In addition, some DNAs with well-defined functions are also increasingly being used. Many become targets for drug action. After the candidate compound is mixed with the target, the interaction between the compound and the target can be quantitatively determined by methods such as enzyme-linked immunofluorescence, fluorescence color development, and nuclear magnetic resonance, thereby becoming the basis for screening compounds. Drug screening at the cellular level is a drug screening model that is closer to physiological conditions. The model is to design target cells for drug action, apply cell culture technology to obtain the required cells, interact these cells with candidate compounds, and interact with biochemical levels. Screening Similar detection techniques determine the ability of a compound to screen it.

The biochemical level of drug screening is relatively simple and the cost is low, but because the role of the drug in the body does not depend only on its degree of interaction with the target enzyme, absorption, distribution, metabolism, excretion will have a great effect on the drug. Influence, only a thin cell membrane can block the way for many candidate compounds to become drugs, so the biochemical level of drug screening has more uncertain factors and higher misscreening rate. Cell-level drug screening models are closer to physiological conditions, and the accuracy of screening is higher, but the need to establish a cell model, the operation is more complicated, the cost is higher, and the parallelism between the data is poor. In addition, due to technical limitations, some targets are still Drug screening at the cell level is not possible. ^[1]

Drug screening classification

High-throughput screening

High-throughput screening was originally a drug screening method that came with combinatorial chemistry. In the late 1990s, the emergence of combinatorial chemistry changed the way humans acquired new compounds. People could synthesize a large number of compounds in a short period of time with fewer steps. In this context, high-throughput screening technology came into being. High-throughput screening technology can screen a large number of candidate compounds in a short period of time. After development, it has become a relatively mature technology. It is not only used for compound screening of combinatorial chemical libraries, but also more for existing compound libraries. Filter. All major drug manufacturers in the world have established their own compound libraries and high-throughput screening agencies to conduct combed screening of compounds that have the potential to form drugs.

A high-throughput drug screening system includes micro and semi-micro pharmacological experimental models, sample library management systems, automated experimental operating systems, high-sensitivity detection systems, and data acquisition and processing systems. The operation of these systems ensures that the screening systems can operate in parallel Search for a large number of candidate compounds. High-throughput screening technology combines the knowledge and advanced technologies of molecular biology, medicine, pharmacy, computational science, and automation technology to become the main way of drug development today. The complete high-throughput screening system is also called a drug screening robot system because of its high level of integration and automation. ^[1]

Virtual drug screening

Virtual drug screening is another direction for the development of drug screening technology. Because physical drug screening requires the construction of large-scale compound libraries, extraction or cultivation of a large number of target enzymes or target cells necessary for experiments, and the need for complex equipment, Huge amounts of money are invested in drug screening. Virtual drug screening is to simulate the process of drug screening on a computer, predict the potential activity of compounds, and then perform targeted physical screening of compounds that are more likely to become drugs, so that Greatly reduce drug development costs.

According to the calculation principle, virtual drug screening is divided into two types: screening based on small molecule structure and screening based on the mechanism of drug action. The model searches the compound database according to the model. This screening technology is essentially a database search technology; the latter mainly uses molecular docking technology. To implement this screening, you need to know the molecular structure of the drug target and calculate the compound by molecular simulation. The ability of small molecules in a library to bind to a target predicts the physiological activity of candidate compounds. Establishing a reasonable pharmacophore model, accurately determining or predicting the molecular structure of the target protein, and accurately and quickly calculating the free energy change of the candidate compound's interaction with the target are the key to virtual drug screening and the bottlenecks that limit the accuracy of virtual screening. Although the accuracy of virtual screening needs to be improved, its fast and cheap characteristics make it one of the most rapidly developing drug screening technologies. ^[1]