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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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Emerging evidence has demonstrated the vital role of metabolism in various diseases or disorders. Metabolomics provides a comprehensive understanding of metabolism in biological systems. With advanced analytical techniques, metabolomics exhibits unprecedented significant value in basic drug research, including understanding disease mechanisms, identifying drug targets, and elucidating the mode of action of drugs. More importantly, metabolomics greatly accelerates the drug development process by predicting pharmacokinetics, pharmacodynamics, and drug response. In addition, metabolomics facilitates the exploration of drug repurposing and drug-drug interactions, as well as the development of personalized treatment strategies. Here, we briefly review the recent advances in technologies in metabolomics and update our knowledge of the applications of metabolomics in drug research and development.
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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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With the advances in medicine, people have deeply understood the complex pathogenesis of diseases. Revealing the mechanism of action and therapeutic effect of drugs from an overall perspective has become the top priority of drug design. However, the traditional drug design methods cannot meet the current needs. In recent years, with the rapid development of systems biology, a variety of new technologies including metabolomics, genomics, and proteomics have been used in drug research and development. As a bridge between traditional pharmaceutical theory and modern science, computer-aided drug design(CADD) can shorten the drug development cycle and improve the success rate of drug design. The application of systems biology and CADD provides a methodological basis and direction for revealing the mechanism and action of drugs from an overall perspective. This paper introduces the research and application of systems biology in CADD from different perspectives and proposes the development direction, providing reference for promoting the application.
Subject(s)
Humans , Systems Biology , Drug Design , Drug Development , Genomics , MedicineABSTRACT
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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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
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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Hemophilia is the only rare hereditary hemorrhagic disorder included in the First Rare Diseases catalogue. However, rare bleeding diseases identified in the clinic are far more common than hemophilia. Most other rare hemorrhagic disorders have less effective treatment than hemophilia. Hemophilia has a history of successful drug development in rare hemorrhagic diseases, and the cycle between clinical research and drug development has been gradually realized. Drug research and pharmaceutical companies can refer to the drug research and development process in the field of hemophilia, learn from the experience of hemophilia drug research and develop treatments. The industry can increase drug development by strengthening basic research, focusing on the value of natural history research, the application of quantitative pharmacological tools and improving the efficiency of drug development to meet the urgent unmet medical needs of patients with rare hemorrhagic diseases.
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@#The progress of molecular biology and tumor biology has greatly changed the mode of cancer treatment. A large number of scientific studies have revealed the mechanism of tumor immune evasion, and a variety of new types of tumor immunotherapy have emerged, which has become another effective treatment of cancer after surgery, radiotherapy, chemotherapy and targeted therapy. This paper introduces the mechanism of tumor cell immune evasion, and focuses on the design principle, biological drugs and the latest research progress of immunotherapy, such as cytokine immunotherapies, therapeutic monoclonal antibody immunotherapy, PD-1/PD-L1 therapy, CAR-T therapy, tumor vaccine, oncolytic virus and so on. At the same time, the advantages and disadvantages of various immunotherapies are compared to provide reference for drug research and development in tumor immunotherapy.
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At the end of 2019,an outbreak of 2019 new coronavirus infectious disease (COVID-19) in Wuhan spread rapidly in China and reported cases in other countries.The number of infected cases and deaths quickly exceeded Severe Acute Respiratory Syndrome (SARS) in a short period of time,resulting in incalculable losses to China.Chinese researchers have quickly identified the pathogen,2019-nCoV (or SARS-CoV-2 or HCoV-19) and carried out the research and development of antiviral drugs at different levels.This article briefly reviews the current advancement of research and development of new therapeutics against 2019-nCoV infection.Given that the progress of research and development of antiviral drugs against the emerging and reemerging pathogens is relatively backwarded,we suggest that the research and development of antivirals against pathogens with pandemic or epidemic potential should be carried out in advance before the occurrence of the outbreaks. At the national level,we should promote the research and development of broad-spectrum antivirals and clinical trials to combat the pathogens with epidemic risk.
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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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A series of incentive policies have been developed by many foreign governments to encourage pharmaceutical companies to develop orphan drugs that have a small market and high research risk. Taking the United States, the European Union and Japan as the representatives, this paper reviews the international management experiences and incentive policies on orphan drug research and development. Current research and development status of orphan drugs in China is also briefly introduced. Based on international experience, some suggestions are put forward on the development of orphan drug research policy in China, in hope of providing references for promoting the establishment of orphan drug incentive policies in our country.
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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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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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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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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.