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Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.
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Premature ejaculation (PE) is the most common male sexual dysfunction with a high incidence, which seriously affects the relationship between a husband and wife and family harmony. Drug therapy is a first-line treatment for PE patients with premature ejaculation, and has achieved good efficacy, but the clinically available drugs are single and the abandonment rate is high. Coupled with the ineffective treatment of some patients, new drug research and development is imminent. This paper systematically reviews the current status of drug treatment for premature ejaculation, focusing on the research and development of new drugs and research progress in order to provide a reference for clinicians.
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There are more than 60 million alcoholic liver disease (ALD) patients in China, which has become a public health problem that cannot be ignored. Moreover, the social problem of "alcohol culture" is still hardly to solve, so that safe and effective prevention and treatment for ALD are in urgent need clinically. Previous studies on ALD have focused on the direct damaging effects of alcohol and its toxic metabolites, while recent studies have shown that the pathogenesis of ALD also include alcohol metabolic reprogramming and endogenous metabolites disorder. Although the endogenous metabolites have no direct toxicity, its long-term effect should not be ignored. These endogenous metabolites could change epigenetic modifications, cause widespread and persistent abnormal gene expression and signal pathway activation abnormally to promote metabolic reprogramming and stamp it as "metabolic memory", which manifest pathological changes and promote ALD, especially liver fibrosis/cirrhosis and liver cancer. Based on this, the article reviews the important epigenetic modifications caused by related metabolites in ALD and their associated effects. The role of traditional Chinese medicine (TCM) and its active ingredients in regulating epigenetics was also analyzed. The results suggest that regulation of epigenetics and alteration of "metabolic memory" may be a novel mechanism of TCM in the prevention and treatment of ALD.
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Design of structurally-novel drug molecules with deep learning can overcome the technical bottleneck of classical computer-aided drug design. It has become the frontier of new technique research on drug design, and has shown great potential in drug research and development practice. This review starts from the basic principles of deep learning-driven de novo drug design, goes on with the brief introduction to deep molecular generation techniques as well as computational tools and the analysis on representative successful cases, and eventually provides our perspective for future direction and application prospect about this technique. This review will provide ideas on new technique research and references for new drug research and development practice to which this technique is applied.
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Due to the infinite proliferation， strong migration and loss of contact inhibition of tumor cells， tumor has become the most intractable diseases to be cured in the world. At present， the main treatments of tumor diseases are surgical resection， radiotherapy， chemotherapy， targeted-therapy and immunotherapy. Although these measures can inhibit or kill the tumor to a certain extent， they still cannot avoid adverse reactions and drug resistance. After thousands of years of clinical practice， traditional Chinese medicine （TCM） has the characteristics of good curative effect， few adverse reactions and significantly improving the quality of life in patients， which provides new ideas for the prevention and treatment of tumors. As an endemic and rare plant in China， Tetrastigma hemsleyanum has been listed in the 2015 edition of Zhejiang Provincial Processing Specification of TCM with the effects of heat-clearing and detoxification， detumescence and analgesia， dissipating phlegm and resolving masses. It has been reported that the chemical constituents of T. hemsleyanum are mainly flavonoids， polysaccharides， phenolic acids， terpenoids， steroids， volatile oils， alkaloids and so on. It can exert a broad spectrum of anti-tumor effects through various ways such as inhibiting proliferation， migration and invasion of tumor cells， inducing apoptosis of tumor cells， inhibiting angiogenesis of tumor cells， reversing multidrug resistance of tumor cells and regulating body autoimmunity. On the basis of reviewing relevant literature at home and abroad， this paper intends to systematically sort out the chemical and anti-tumor research of T. hemsleyanum， and in order to provide a new idea for its synergistic anti-tumor effect of multi-component， multi-pathway and multi-target， and finally provide theoretical basis for the research and development and clinical application of new anti-tumor drugs of T. hemsleyanum.
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As lung cancer targeted therapy and immunotherapy drugs are the current hot spot in the research and development area of new anti-tumor drugs, the amount of clinical trial in this area is increasing year by year. On the basis of combing the on-site inspections of drug registration clinical trials from 2019 to 2021, combined with the characteristics of lung cancer targeted therapy and immunotherapy drugs, this paper discusses the focus of on-site inspection of clinical trials of such drugs, and puts forward suggestions for the compliant implementation of lung cancer clinical trials. .
Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Immunologic Factors/therapeutic use , Immunotherapy , Lung Neoplasms/drug therapy , Molecular Targeted TherapyABSTRACT
The experienced prescriptions of famous prestigious Chinese physicians are effective prescriptions developed by prestigious Chinese doctors during their long-time clinical practice, which reflect the traditional Chinese medicine (TCM) understanding of the disease development regularity and core pathogenesis. These experienced prescriptions provide valuable experience for medication and prescription regularities, and represent the highest level of TCM treatment and the major sources of new drug research, development and technology innovation. It is of great significance to inherit academic thoughts and clinical experiences of prestigious Chinese physicians, explore and summarize experienced prescriptions, and develop new Chinese drugs. The researches of new drugs based on experienced prescriptions are the major direction encouraged by the government, with the maximum amount of new TCM drug applications but a low approval rate in recent years. The main reason for the low number of approved new TCM drug applications is that researchers know less about evaluation concepts and relevant techniques, leading to problems in research and development strategy. To facilitate a smooth advance of the new drug research and development and take full advantage of the experienced prescriptions, in this paper, we focus on the problems about new drug development of experienced prescriptions, lay emphasis on the new TCM drug research and development concepts of clinical value, history of human application and whole-process quality control, and deeply and systematically analyze concerns in such links as pharmacy, pharmacodynamics, toxicology and clinic application. The purpose of this article is to provide the reference in solving actual problems, the reliable basis of further researches on experienced prescriptions, and the important guarantee for developing more safe, effective and high-quality controllable drugs to meets clinical requirements, so as to achieve the strategy of a healthy China.
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This article is to investigate the role of international academic communication of pharmacology in scientific and technological innovation. The object, the organization mode and the characteristics of international conferences of pharmacology, as well as their effects on pharmacology, were researched and analyzed. As shown in the text, international academic communication plays a key role in promoting scientific and technological development, such as pharmacological theory and technological creativity, new drug research and development, talents cultivation , etc. On the basis of the analysis, this paper suggests how to promote scientific and technological innovation, talents cultivation, and international discourse power through international academic exchange.
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The ethical issues are different at different research stages of drug discovery.At the preclinical trial phase,laboratory animals are indispensable.The medical animal ethics committees need to approve and supervise animal testing during the experiment whether it adheres to the principles of animal protection,animal welfare principles and ethicalprinciples.At the phase of clinical trials,the subject of drug is human.The medical ethics committee should take full account of the ethical issues arising from the special medicine,special populations and disease in the process of trial and formulate detailed and feasible clauses,thus to ensure the scientificity of the trial and the rights and interests of subjects and promote new drug discovery and integrate with international standards.
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OBJECTIVE:To provide reference for improving the registration success rate of new drug research and develop-ment(R&D)enterprises after adjusting drug registration system in China. METHODS:The national drug policies,regulations and related documents were comprehensively studied and combed to explore the main contents of drug registration system adjustment and its effects on the R&D forms,drug patent and on-site verification. The suggestions were put forward. RESULTS & CONCLU-SIONS:The adjusted drug management system showed new definitions for new drugs and generic drugs in China,as well as de-tailed requirements and regulations for drug R&D conditions,process and on-site inspection. It enhanced the protection of patents and patentees. The new drugs should be assessed its market value and clinical advantages. Data contents and requirements for drug registration declaration were made the relevant adjustments. New drug R&D enterprises should develop drug listed license manage-ment system as early as possible based on the implementation of listed license management system pilot,improve its efficiency and benefit. The new drug R&D should notice the clinical efficacy and demand of market,focus on the drugs with good clinical effica-cy in common diseases,frequently-occurring diseases and major diseases;and those for treating rare diseases,the elderly and chil-dren disease can use easy access or fast track to accelerate the speed of drug registration. New drug R&D enterprises should im-prove the R&D conditions,and standardize the management of development process to ensure the effective and smooth develop-ment.
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Objective Risk management is one of the strong measurements to ensure the conduction of new drug research and development (R&D) projects .Therefore ,establishing a set of evaluation index system in the new drug R&D projects is of great significance to increase the project success rate .Methods By analyzing more than 20 new drug R&D projects of “the mil-itary science and technology major projects”in five years ,the risk factors were induced ,sorted and summed up ,and a set of e-valuation indicator was built up through Delphi method and experts interview .The quantitative study was completed through fuzzy comprehensive evaluation method .Results According to the different stages of new drug R&D projects ,the risk assess-ment indictors and their weight were established .Conclusion These indicators are more objective and accurate which contrib-ute to the risk control in the process of new drug R&D projects .
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Unlike terrestrial organisms, marine organisms have to adapt to extreme marine environmental conditions, and to acclimatize to these conditions, marine organisms possess unique characteristics that differentiate from terrestrial organisms in many aspects, such as metabolism. And this led to marine organisms often produce unique secondary metabolites that have not been observed in terrestrial organisms. Diversity of marine natural products has played a fundamental role in biomedical research and drug development during the last decades, either directly as drugs or as leading compounds that were further optimized by medicinal chemists. From these efforts, 10 approved drugs and dozen current clinical trial agents have been discovered, either as natural products or molecules inspired from the natural product structure. This paper summarized the new drugs developed from marine organisms. This is one of the series papers about "historical story on natural medicinal chemistry".
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Since entering the 21st century,the trend of high incidence of chronic diseases in the in?ternational community has not been effectively controlled and the pharmaceutical and medical fields are put forward new challenges. Both the development and evaluation of chemical drugs,biological drugs or traditional Chinese medicine are facing with how to significantly improve the efficacy and reduce the side effect of the drugs. With the coming of the accurate medical treatment as well as the big data era,new opportunities and challenges are needed either in the development of new drugs or new use of old drugs. However,as known that the human body consists of the symbiotic microbial groups of human microecological system especially the gut microecology system is more and more important in human health and disease,and even part diseases such as obesity and diabetes have a certain degree of causality with the gut microflora,so we need to reanalyze the core ideas about drug development or even the current medical theory system. Therefore,it is possible to step out of the old way of current drug development in the new period,to make new contributions on the real effective implementation of prevention and control of chronic diseases. According to international human body microecological especially the research progress of gut microecological field,systematic analysis of the problems existing in the current research and development of new drugs,will not only focus on the human body itself,but also the human microecology as well as the balance between human and micro?ecological,which will promote rapid development of research and development of new drugs and prevention and control of chronic disease in order to improve the physical and mental health services in our country.
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OBJECTIVE:To provide new strategies and ideas to breakthrough dilemma on new drug research and obtain good drug. METHODS:Source and dilemma on drug discovery and development were analyzed,and new strategies were provided to solve it, and the role of clinical pharmacy work in the drug discovery was analyzed. RESULTS:Compared with its traditional strategies, clinical verification and big strategies in drug discovery had advantages in reducing risk,cutting input and shortening the period of new drug research and development. Clinical pharmacy work will provide strong support for the new strategy of drug discovery. CONCLUSIONS:Drug discovery should transform to clinic-based patterns,and it requires the tightly bonding between the pattern and clinical pharmacy work.
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The seminar on novel ideas and methods in pharmacological researches,and new drug research and development of traditional Chinese medicine(TCM),organized by the Professional Committee of Pharmacology on Traditional Chinese Medicine and Natural Medicine, Chinese Pharmacology Society,was held in Tengzhou,Shandong Province,on August 5,2016. Professor ZHANG Yong-xiang,chair of the committee,presided over the seminar. Professor LIU Jian-xun and LI Lin delivered keynote speeches. More than 30 members of the committee from all over the country attended the seminar. The participants had a broad and in-depth discussion on issues concerning phar?macological researches and new drug research and development of TCM. The ideas and proposals by some committee members were summarized,hoping to provide reference in the pharmacological researches and new drug research and development of TCM.
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The four properties theory of traditional Chinese medicine (TCM) is an important basis for the guidance of TCM clinical medication.However,TCM modernization has produced a large number of active substances with unknown medicine properties.Therefore,it is urgent to build a new drug development system guided with TCM four properties theory.From the view of that four properties of TCM must have their material basis,and based on the known knowledge on TCM four properties,this paper proposed strategies of new drug research by cloning TCM partial components based on theTCM model of standard level property. A certain number of representative standard level property TCM drugs were selected to conduct system separation for the establishment of aTCM model of standard level property with the proportion and content of each separated component as a reference.The standard model was used as a boundary.Contents and proportions of the experimental TCM separation components deviated from thisstandard model were classified as hot or cold properties.From cloning of the partial components of TCM with hot or cold property medicine,the quality standards of partial components of experimental TCM were also studied,in order to investigate their corrective actions and mechanisms.The TCM partial components were expected to form a new TCM drug with the four properties theory of TCM as guidance.
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As the main force of new drug research and development (R&D) in China,pharmaceutical universities are in charge of developing new drugs with our own intellectual property rights.The concept of translational medicine provides opportunity and challenge to improve the efficiency of new drug R&D.Several translational medicine centers have been set up in pharmaceutical universities,which provide practical conditions for new drug R&D in domestic.Administration management approaches to promote new drug R&D in translational medicine platform are analyzed in the paper.
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The vigorous advance on modernization of Chinese materia medica (CMM) has achieved great successes, which is the consensus of scholars. However, the physicians and populace have few awareness of the CMM modernization achievements. It is in great need to promote the modernization of CMM into clinic by translational medicine. The research pathway of CMM translational medicine could be summarized as a repeated cycle of bedside to bench to bedside. And, its main research might include two missions, one is the clinic-oriented standardization of CMM and the other is the clinic-derived discovery of CMM new drugs. The clinic-oriented standardization of CMM is focusing on the development of the effect-based evaluating methods and standards on CMM quality and drug property and promoting CMM integration of "species-quality-property-effect- usage", which aims at making doctors be able to comprehend and emply the CMM standards. The clinic-derived discovery of CMM new drugs diverges into two pathways: one is the development of traditional compound formula drugs based on the physicians' experiences and evidence-based medicine; the other is the innovation of modern multi-component CMM drugs based on the clinical specimens and -omic techniques. The clinic-derived drug discovery provides an efficient approach to develop novel CMM drugs with superior efficacy and safety to traditional ones. Thus, it is reasonable to suggest that the related administrations of state should strongly support the translational research of CMM by granting scientific research projects, training specialists of translational medicine, and reforming the regularities of new drug evaluation and relative policies.
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The new drug research and development(R&D) platforms are comprehensive, open and continuously developing organic systems which integrate such elements as technologies and standards related to the R&D of innovative drugs and serve as pilars and integration media. These platforms are macroscopic and integrated at the governmental level, large and systematic in big pharmaceutical enterprises and research institutes, and detailed and professional in medium and small enterprises. The construction of new drug R&D platforms in China experienced germination and rudiment stages during "9th Five-year" period, and has now entered the full-fledged developing stage with the support of Scientific and Technological Major Special Project - "Key New Drugs Creation and Manufacturing", and has evolved from single technological R&D centers to integrated technology platforms with complete pipelines. By comparing the development of domestic and international new drug R&D platforms, this paper puts forward some suggesions on how to develop and manage the Chinese platform and examines its future prospects.
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This paper reviews the recent research progress on the utilization of natural drugs against nonalcoholic fatty liver diseases(NAFLD)and alcoholic fatty liver diseases (AFLD). A total of 122 species of natural drugs, confined to the effective extracts of single herbal or animal drug and the active single natural products, were summarized and categorized as alkaloids, total flavonoids and total phenolics, single phenolics, terpenoids and steroids, total glycosides and total esters, amino acids and heterocycles, polysaccharides and proteoglycans, polypeptides/glycopeptides and poly-unsaturated fatty acids, coumarins and phenomens, single herbal drug, animal and fungus drugs. The future tendency of new natural drug research and development against NAFLD and AFLD is also discussed and some afforded suggestions were provided.