Classification of drug screening, definition of drug screening

High-throughput screening was originally a drug screening modality that arose with combinatorial chemistry. In the late 1990s, the advent of combinatorial chemistry changed the way humans obtained new compounds, allowing people to synthesize large quantities of compounds simultaneously in a short period of time in fewer steps. High-throughput screening technology can complete the screening of a large number of candidate compounds in a short period of time, and has become a relatively mature technology, which is not only used for compound screening of combinatorial chemical libraries, but also more widely used for the screening of existing compound libraries.

The world's major drug manufacturers have established their own compound libraries and high-throughput screening institutions to conduct grate-comb screening of compounds with potential to form drugs.

A high-throughput drug screening system includes micro and semi-micro pharmacological experimental models, a sample bank management system, an automated experimental operating system, a high-sensitivity detection system, and a data acquisition and processing system, which ensure that the screening system can search for a large number of candidate compounds in parallel. High-throughput screening technology combines knowledge and advanced technologies from molecular biology, medicine, pharmacy, computational science, and automation technology to become the dominant modality of drug development today. Due to its high degree of integration and automation, the complete high-throughput screening system is also known as the "drug screening robotic system".

Virtual drug screening is another direction of drug screening technology development, because the physical drug screening needs to build a large-scale compound library, extract or cultivate a large number of target enzymes or target cells necessary for experiments, and need complex equipment support, so the physical drug screening needs to invest a huge amount of money, virtual drug screening is to simulate the process of drug screening on the computer, make a good decision on the possible activity of the compound, and then carry out targeted solid body screening on the compounds that are more likely to become drugs. This can dramatically reduce drug development costs.

According to the principle of calculation, virtual drug screening is divided into two categories: screening based on small molecule structure and screening based on drug mechanism of action, the former is based on the quantitative structure-activity relationship study of compounds known to have the same mechanism of action, draws the pharmacophore model of the drug, and searches the compound database according to the model, which is essentially a database search technology; The latter mainly applies molecular docking technology, and the implementation of this screening requires knowing the molecular structure of the target of drug action, calculating the ability of small molecules in the compound library to bind to the target through molecular simulation, and the physiological activity of candidate compounds. Establishing a reasonable pharmacophore model, accurately determining or optimizing the molecular structure of the target protein, and accurately and rapidly calculating the free energy changes of the interaction between candidate compounds and targets are the keys to virtual drug screening, and they are also the bottlenecks that limit the accuracy of virtual screening. Although the accuracy of virtual screening needs to be improved, its fast and inexpensive characteristics make it one of the fastest-growing drug screening technologies.

At present, drug screening is done from in vitro and in vivo

1. Some only have a small number of compounds, and if conditions permit, they will be screened directly in animals.

2. Generally speaking, the first thing to do is in vitro screening. The lead activity screening method is simply to do in vitro activity screening.

First, if it is a compound synthesized by yourself or isolated and purified from natural products, it is necessary to conduct follow-up screening, and if it does not involve the target, use the cell level to do in vitro experiments;

Second, if it involves the target, see whether it is an inhibitor or agonist, there are several situations, if you don't know what protein target, then the head is big, you have to read the relevant information, full research, and then see what the possible targets are, to test, now computer-based reverse target finding and biological experiment-based kinase profiling test are two of the alternatives, in addition to kinases, of course, there are other proteases; If you know the specific target, then it's easy to do it, just go straight to the test. In short, the judgment is still based on the results of biological experiments.

Broadly defined: It is the process of drug optimization within a certain selectable range through appropriate methods and technologies, including genomics, proteomics, metabolomics, computational biology, biochip technology, microfluidic chip technology, etc., according to specific requirements and purposes. Therefore, drug screening includes prescription screening in the process of new drug research, and the selection of drugs that meet the requirements according to a specific purpose.

Narrow sense: screening refers specifically to the use of experimental techniques.

In fact, drug screening also includes drug screening in vivo, which now involves a wide range, from virtual screening to biological experiment screening.

Drug screening refers to the process of assessing the biological activity, pharmacological effects, and medicinal value of substances (sampling) that may be used as drugs using appropriate methods.