After the exchange of the 9th National Youth Pharmacists' Latest Scientific Achievements Exchange Conference, Professor Wang Xiaoliang, Vice President of the China Pharmacy Association and the Institute of Pharmacy, Chinese Academy of Medical Sciences, presented all the young pharmaceutical science and technology workers at the conference with the title "New Drugs." R&D Situation and Opportunities: Invited Report. In his report, he particularly emphasized that young pharmaceutical science and technology workers should broaden their R&D ideas and pay attention to the research and development of multi-target drugs.
The discovery of new targets is limited. It is reported that the discovery of new targets is a key bottleneck restricting the development of new drugs in China and even in the world. Over the past period of time, researchers have found that the speed of drug targets is very fast. At the beginning of this century, about 480 new target targets at the molecular level were discovered. With the completion of the Human Genome Project, it is predicted that more than 3,000 new drug targets will be discovered. However, the new target actually found is very limited, still about 500 or so. Therefore, the discovery of new drug targets remains an important task for drug developers.
Single target drug is unreasonable. Professor Wang Xiaoliang said that at present, China is facing the challenge of a huge public health problem, and new drug development should also focus on important areas such as cancer, central nervous system diseases, and metabolic diseases, as well as anti-infection, Other areas such as cardiovascular diseases. With the deepening of research on molecular mechanisms related to diseases and the rapid development of modern drug development technologies represented by drug target research, high-throughput drug screening, and combinatorial technologies, there are more and more drugs targeting a single molecular target, and some Play a significant effect in clinical practice. However, there are many problems with the active compounds found on a single target, such as poor drug-making or side effects, and single-target drugs still have irrationality. For example, in most cases, especially diseases of the central nervous system, its etiology, pathological mechanism, and disease progression process are very complex, and are usually multi-factorial, including signaling pathways in which many risk factors and defective proteins lose balance with each other, if the drug only acts on On a single target, the success rate of treatment is extremely low. In addition, a drug can target pleiotropic cytokines or other proteins with multiple physiological functions that can cause multiple normal cellular pathways to be affected at the same time.
Looking for multi-targeted drugs to become a trend Professor Wang Xiaoliang believes: "Finding multi-targeted drugs is the current trend." He stressed that a good drug does not act selectively on a single target, but on multiple targets. Several abnormal proteins that act on the etiology, pathology, and disease progression, or proteins that act on the re-equilibration of certain factors should be targeted. When conducting multi-target discovery of new drugs, it should be noted that the affinity between the drug and the target does not have to be strong, but rather moderate and less toxic. In addition, we must also pay attention to the overall animal experimental research.
At present, many old medicines used in clinical practice actually act on multiple targets, and the actual results are very good. He used antiarrhythmic drugs as an example to show that although people developed various drugs such as sodium channel blockers and potassium channel antagonists, the most effective one was found to be amiodarone, which acts on multiple targets.
Multi-target drugs are not equal to compound drugs. It has been suggested that if this is the case, then eat three or five medicines and let them act on different targets instead of on the line? This point of view, Professor Wang Xiaoliang corrected that, in fact, multi-target drugs are not equivalent to compound drugs, and the results are not the same. Each of the three or five drugs in the compound has its own specific plasma protein binding ability. Each drug selectively competes with a liver drug enzyme for metabolism. These binding and metabolic processes affect each other. The multi-target drug is a different molecule within a molecule acting on different targets at the same time, its own physicochemical characteristics is a single, will not affect other drugs.
Professor Wang Xiaoliang emphasized that pharmaceutical science and technology workers should broaden the thinking of drug development and should consider more than a few multi-target drugs. In practice, consciously design two groups or three groups of a molecule to play a role in different targets. .
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