Drug screening model is an important condition for discovering new drugs. The establishment of new models will drive the emergence of new drugs. The development of molecular biology, cell biology, and computer science, especially the completion of the Human Genome Project, has brought good opportunities for medical research, and also provided many aspects such as theory, technology, and materials for the establishment of new drug screening models. Advantage. Therefore, we should make full use of the development technology of various disciplines to establish more new screening models to promote the discovery of new drugs.
Drug screening must first have a suitable screening model. Drug screening model is an experimental method used to prove that a substance has pharmacological activity (biological activity, therapeutic effect). These experimental methods are one of the important conditions for finding and discovering drugs. In the long-term practice of finding drugs, people have established a large number of models for screening new drugs, which have played an active role in the discovery and research of new drugs. The study of drug screening models has gone through three different stages of development: the overall animal model, the screening model at the level of tissues and organs, and the drug screening model at the cellular and molecular levels. Each model originates from the birth of a new technology. These models have their own pros and cons, and we should choose the appropriate model according to the specific experiment.
Whole animal model
The overall animal model is to use animals as the observation object of drug screening, to prove the pharmacological effects of certain substances and evaluate their medicinal value by the animal’s response to drugs. Since normal animals cannot fully reflect the therapeutic effect of drugs under pathological conditions, more animal pathological models are used in drug screening. The basic conditions that an ideal animal model should possess are the similarity of the pathological mechanism to human diseases, the stability of the pathological manifestations, and the observability of drug effects.
The advantages of the overall animal screening model: it can intuitively reflect the therapeutic effect, adverse reactions and toxic and side effects of the drug from the animal. The screening results obtained from animal models are very important for predicting the clinical effects, toxic and side effects and application prospects of the screened samples.
Disadvantages of the overall animal screening method: Due to the particularity of the animal, the drug screening process mainly depends on manual operations, and only limited samples can be screened, which makes the animal model screening of new drugs have obvious limitations, low efficiency and high cost .
Screening model of tissue and organ level
With the development of modern medicine and modern pharmacology, more and more drug screening models are prepared using animal tissues and organs, such as in vitro blood vessel experiments, heart perfusion experiments, tissue culture experiments and other methods. By observing the effects of drugs on specific tissues or organs, the principle of drug action and possible pharmacological effects can be analyzed. The screening model at the level of tissues and organs can reflect the action of drugs under physiological conditions, and can also be prepared as a pathological model to observe the effects of drugs on tissues and organs under pathological conditions. Screening drugs using tissue and organ models is a major advancement in drug screening technology.
The advantages of isolated tissue and organ models: reduce the amount of screening samples; reduce labor intensity and expand the scale of screening; reduce the amount of animals, especially some models only use a small part of tissues and organs (such as the blood vessel strip test method), at the same time Multi-sample screening improves screening efficiency and reduces screening costs; it reduces factors that affect drug action and makes it easy to evaluate drug action.
The shortcomings of applying the screening model at the level of tissues and organs: small scale, low efficiency, limited drug reaction, and difficult to achieve one drug and multiple screening. In addition, the high technical requirements of manual operation is also one of the main reasons affecting its application in drug screening.
Cell and molecular level drug screening model (high-throughput drug screening)
Due to the rapid development of molecular biology technology and cell biology technology in recent years, molecular pharmacology research has also continued to deepen, new drug targets, functional proteins, gene expression changes, biological active ingredients, etc. have been continuously discovered to provide drug screening A large number of new targets, such as new receptors and enzymes. These new targets provide new information and opportunities for new drug screening. The application of the drug screening model at the cellular and molecular level has laid the foundation for automated operations, and has transformed drug screening from the traditional manual screening form to a new technology system of computer-controlled automated large-scale screening, forming a high-throughput drug screening.
High-throughput drug screening uses automated screening systems to complete thousands of or even tens of thousands of compound sample activity tests on specific screening models in a short time. Generally speaking, the daily screening capacity should be above 10,000 times, which can be called high-throughput screening.
Fast-Screen tens of thousands of medicines every day
Micro-Requires micrograms for screening samples
Sensitive-accurately determine the activity and selectivity of the screening sample
Economical-low screening costs
The advantages of high-throughput drug screening: the realization of large-scale drug screening, the use of medicinal material resources to a greater extent, the probability of drug discovery is increased, and the quality of new drug discovery is also improved; the screening experiment is in the micro screening system Completed, the sample dosage is generally in the microgram level (μg), which saves sample resources, lays the material foundation of “one drug and multiple sieves”, saves experimental materials, and reduces the cost of single drug screening; high-throughput drug screening is highly Automated operation reduces the occurrence of operation errors, reduces labor intensity, and improves the efficiency of drug screening and the accuracy of results; it has the characteristics of multidisciplinary theory and technology.
Disadvantages of high-throughput drug screening: The high-throughput screening mainly uses in vitro experimental models at the molecular and cellular levels. No model can fully reflect the full pharmacological effects of drugs; the models used for high-throughput screening are always limited Therefore, it is also unrealistic to establish an ideal model that reflects all the physiological functions of the body or the action of drugs on the whole body.
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