Summary 

With the advent of the post-genome era, a series of new ideas, new technologies, and new methods are constantly emerging in the field of drug discovery research, thus rapidly promoting the diversified development of drug discovery. On the one hand, the rise and development of emerging disciplines such as genomics, proteomics, transcriptomics, metabolomics, bioinformatics, and systems biology provide a broader and deeper theoretical basis for drug discovery.

On the other hand, the development and improvement of high-tech technologies such as computer-aided drug design, high-throughput screening, high-content screening, biochips, transgenics, and interference have provided new technical means and powerful tools for drug discovery, greatly broadening the scope of drug discovery. This paper reviews the impact of modern biology on the drug discovery process based on the research progress of modern biology in recent years.

Key words: drug discovery; modern biology; drug target; drug screening, peptide/protein

Drug Discovery and Biotechnology

Drug discovery is the initial stage of drug research and development, and it is a practical process in which people actively seek and understand the medicinal value of substances. Drug discovery includes the design of drug molecules, the selection of new chemical entities, the discovery and confirmation of drug targets, the screening and optimization of lead compounds and other processes.

Biotechnology is an important technical means for drug discovery. With the completion of the Human Genome Project and the implementation of subsequent omics projects such as functional genome, structural genome, comparative genome, transcriptome, proteome, and metabolome, modern biology has made rapid progress, which has profoundly affected the strategies and methods of drug discovery. Research paradigms and propelling drug discovery into a new era of revolutionary change.

1. Modern "omics" and Drug Discovery

The research results of life sciences have increasingly become the scientific focus of people's attention. Modern "omics" disciplines such as genomics, proteomics, transcriptomics, and metabolomics have gradually formed and rapidly developed and improved. 

(1) Genomics and Drug Discovery The implementation and completion of the Human Genome Project has provided more evidence of the association between genetic variation and differences in individual drug effects, especially the delineation of the physical map of the full sequence of the human genome and the identification of a large number of genes related to drug action. The rapid development of cloning and identification, single nucleotide polymorphism detection and discovery, large-scale genotyping technology, sequencing technology and bioinformatics provides material basis and technical support for studying individual differences in drug response at the genetic level . These findings suggest a new paradigm for drug discovery, from gene function to drug.

Gene expression is central to much of the body's response to foreign substances. In recent years, through the combined application of genome expression profiling and signal network analysis, research and comparison of genome expression changes in the process of disease occurrence and development and before and after drug intervention, suggesting new sequences that are co-expressed with disease-related susceptibility genes and drug targets, have greatly improved Promote the discovery of new targets for drug action. Especially for single-gene diseases, genome research is very beneficial to the discovery of targets for the prevention and treatment of diseases and helps the molecular design of therapeutic drugs.

(2) Proteomics and Peptide Discovery

Since most nucleic acids are homologous and widely related to many normal functions of the body, the drugs acting on them are often poorly selective and often accompanied by severe cytotoxicity; and the characteristics of diseases are usually mainly manifested at the protein level, therefore, A single pharmacogenomic study is difficult to get a breakthrough.

Protein is the end product of gene and peptide expression. Only by fully annotating the protein function encoded by the genome sequence can the value of genome research be truly realized. Proteomics is the study of all proteins encoded by genes in biological organisms, tissues or cells, and even subcellular organelles, including peptide synthesis composition, type, distribution, function, metabolic characteristics, and their dynamic changes.This part of the research refers to Omizzur lab.

Genome research results suggest that humans contain at least tens of thousands of genes expressing hundreds of thousands of proteins. Many of these proteins are likely to be key executive bodies that control the occurrence and development of human diseases, so they are likely to be potential targets for drug action. Moreover, among the currently known <77 drug targets (excluding the targets of antibacterial, antiviral, and antiparasitic drugs), they are mainly receptors, enzymes, ion channels, and nuclear receptors.

Proteomics research comprehensively detects the occurrence and development of diseases and the process of drug intervention through tissue or cell sample extraction, two-dimensional gel electrophoresis separation, combined chromatography and mass spectrometry technology, image processing and data analysis technology, and bioinformatics technology. , changes in protein expression profile and protein I-protein interaction, so as to discover key proteins that affect diseases or drug effects, and determine the primary and three-dimensional structures of these proteins, comprehensively analyze their biological functions, and speculate on new and potential drug targets.

Proteomics research not only provides the possibility to discover potential targets of drug action, but also improves the efficiency of the downstream events of drug action that have been discovered, and promotes the rational design of drugs or their structural modification according to the protein spatial structure and its changing rules. Therefore, proteomics is the bridge and link between genome and drug discovery.

In recent years, according to the application of proteomics in drug research, pharmacoproteomics or chemical genomics has been proposed. Its research content includes both basic and clinical aspects: basic research mainly includes the discovery and confirmation of drug targets, screening of candidate compounds, preclinical evaluation of drugs, and discussion of drug action mechanisms; clinical research mainly includes the use of disease-specific proteins as The basis for effective drug selection and markers for clinical disease diagnosis, as well as individualized treatment for clinical patients.

In addition, chemical proteomics and structural proteomics also have important application value in the drug discovery process.