The brain-derived neurotrophic factor in neuronal plasticity and neuroregeneration: new pharmacological concepts for old and new drugs

Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neurogenesis to recover neuronal defici even in adulthood.

New drugs for the treatment of metastatic colorectal cancer

Colorectal cancer(CRC)represents one of the most frequent malignancies in terms of incidence and mortality,thus representing the third leading cause of cancer death worldwide.In the last decade,few drugs have enriched the treatment landscape of metastatic CRC and have significantly affected prognosis.Unlike other neoplasms,metastatic CRC patients who have exhausted treatment options often still maintain a good performance status.There are many challenges to increasing potential treatment options,notably a better understanding of disease biology and the mechanisms of resistance underlying cancer treatment failure.The development of new drugs for metastatic CRC certainly represents one of the most important challenges in medical oncology.This article discusses the main limitations in the development of new drugs and potential future scenarios.In particular,we addressed three questions:(1)The main limitations of targeted therapy in the treatment of metastatic CRC(mCRC);(2)New target armamentarium that could escape primary and secondary resistance and lead to more personalized mCRC therapy;and(3)Future directions.

Literature Review on the Development of New Drugs Based on TRIZ

Objective To promote the application of TRIZ theory in the new drug R&D and the innovative development of medical devices.Methods TRIZ can be literally translated as“theory of inventive problem resolving”,focusing on clarifying and solving contradictions in the system.This article introduces the TRIZ theory and the general process of new drug development.It collects literature in the field of new drug development and medical devices and refers to ideas for solving problems in some successful cases of applying TRIZ theory in other fields.Results and Conclusion After summarizing the general ideas of TRIZ to solve the problems,it is concluded that attention should be paid to applying TRIZ theory in the development of new drug and medical devices.

Opinion on pharmacology research and new drug development from precision medicine

Since President Obama announced the Precision Medicine Initiative from a national strategy perspective in his State of the Union address,precision medicine has rapidly become a world-wide hotspot and drawn global attention in the medical field.Precision medicine aims at applying genetic information of individual diseases to guide his or her diagnosis and treatment.

PREDICTION OF THE THERAPEUTIC EFFECTIVENESS OF NEW DRUGS FROM CLINICAL PHARMACOLOGY STUDIES

The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years from the time of patenting are required to make a new drug available for general prescription. Every new drug needs to be charac-

Real-World Evidence Supporting New Drug Review and Approval in European Union and Its Enlightenment to China

Objective To analyze the application of real-world evidence(RWE)in the field of medicine in European Union,and provide suggestions for RWE supporting the review and approval of new drugs in China.Methods The European Medicines Agency(EMA)and other databases were used to search relevant documents for analyzing the European Union’s new drug review and approval process with the support of RWE.Results and Conclusion The European Union carrying out new drug review and approval with the support of RWE has just begun.The decision-making process includes three stages such as new drug research and development,review,and approval.However,there are some challenges in data quality,research methods,evidence sufficiency,and research process of RWE supporting the European Union in reviewing and approving new drugs.At present,RWE can accurately grasp the clinical effects of drugs and improve the safety and effectiveness in the process of assisting the review and approval of new drugs.At the same time,RWE also can promote the development and application of Traditional Chinese Medicine(TCM)and help find out the potential value of TCM such as new indications.

Application Research of Earned Value Management in New Drug Research and Development Projects

Objective To help investors assess and control the costs of new drug development and reduce the risks of new drug development projects.Methods Cost analysis and financial forecasting were carried out with the integrated approach of earned value management.According to the principle of earned value management deviation analysis,the basic process of the new drug research and development project was combined with the hypothesis method from the research of Tufts Drug Development Research Center.Results and Conclusion If the project progress check was carried out in the clinical trial,the project costs were found overspent,the efficiency was low,the project progress was faster,and the resource investment was ahead.It is recommended that the adjustment should be made to reduce the input of resources,and increase the efficient key personnel to take the place of some less efficient staff.

The CAS System of New Drug Research and Its Key Results

The Chinese Academy of Science (CAS), the top national research hub for natural sciences, has always been committed itself to the national target of research and development (R&D) of new medicines. During the past several decades, a great number of R&D achievements have been attained. During the period from 1986 to 1999, for example, 135 pharmacutical projects won prizes of the CAS awards for natural sciences, inventions and S&T progress (roughly ac-

Establishment of an internationally recognized platform for the communication of pharmaceutical researches supported by the National New Drug Innovation Programs ——Experiences and goals of the Journal of Chinese Pharmaceutical Sciences

The initiation of the National New Drug Innovation Key Technology Program marked a strategic shift of new drug discovery in China, which will greatly enhance the new drug discovery research activities. It presents a valuable opportunity for the growth and quality advancement of pharmaceutical science journals. As the only comprehensive English journal of the Chinese Pharmaceutical Association, In the new situation, Journal of Chinese Pharmaceutical Sciences （JCPS） plays a critical role in the communication of new discoveries in pharmaceutical researches to the scientific community. To fulfill the roles as an internationally recognized platform for the communication of the new drug discoveries supported by the National New Drug Innovation Programs, the JCPS editorial office will take advantage of its English language specialty, emphasize quality and digital access, and promote the advancement of the journal.

Developing new drugs from annals of Chinese medicine

Developing new pharmaceuticals requires massive amounts of time,money and efforts.The key step is how to find a safe and effective entity for a disease condition and how to develop it as new drug effectively.Unfortunately,the FDA’s rate of approving new entities has declined dramatically in the last three decades.There is a strong need to review the current strategy and to optimize process in developing new drugs,both to shorten the process and increase the success rate.Chinese medicine has used natural products to treat patients for thousands of years,and Chinese medicine practitioners have chronicled the patients and treatment methods for thousands of years.There is much information that has not yet been used.The success stories of artimisinin and arsentic trioxide are wonderful examples of how the annals of Chinese medicine can provide leads for discovering new drugs.This paper argues that the annals of Chinese medicine are valuable and describes how they can be used in modern drug discovery.The major topics addressed are:(i)why Chinese medicine is a rich resource for finding new drugs;(ii)how to identify a potential valuable record from Chinese medicine annals;(iii)when a potential valuable record is identified from annals,how to proceed;and(iv)both why and how the approach used for chemical drugs should be revised for drugs based on the historical documents related to herbal medicine.In conclusion,we argue here that the annals of Chinese medicine offer not only a rich resource for new drugs,but also several centuries of patient data with regard to safety and efficacy,that in effect represent pilot studies.Acknowledging and using these data can shorten new drug discovery time and improve efficiency of the drug development process,bringing more effective,safe drugs to market much more quickly and cheaply.

Harnessing the cyclization strategy for new drug discovery

The design of new ligands with high affinity and specificity against the targets of interest has been a central focus in drug discovery.As one of the most commonly used methods in drug discovery,the cyclization represents a feasible strategy to identify new lead compounds by increasing structural novelty,scaffold diversity and complexity.Such strategy could also be potentially used for the follow-on drug discovery without patent infringement.In recent years,the cyclization strategy has witnessed great success in the discovery of new lead compounds against different targets for treating various diseases.Herein,we first briefly summarize the use of the cyclization strategy in the discovery of new small-molecule lead compounds,including the proteolysis targeting chimeras(PROTAC)molecules.Particularly,we focus on four main strategies including fused ring cyclization,chain cyclization,spirocyclization and macrocyclization and highlight the use of the cyclization strategy in lead generation.Finally,the challenges including the synthetic intractability,relatively poor pharmacokinetics(PK)profiles and the absence of the structural information for rational structure-based cyclization are also briefly discussed.We hope this review,not exhaustive,could provide a timely overview on the cyclization strategy for the discovery of new lead compounds.

Regulatory evaluation of efficacy and safety of new drugs in China

Accessibility, availability, and rational use of medicines are widely recognized priorities for guaranteeing equity in health care. Commercial pressure can twist health policy if pharmaceutical companies are allowed to promote and impose their products beyond clear public-health interest. National regulatory

New strategies against drug resistance to herpes simplex virus

Herpes simplex virus （HSV）, a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir （ACV） and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets （the DNA helicase/primase （H/P） complex）, new types of molecules （nature products） and new antiviral mechanisms （lethal mutagenesis of Janus-type nucleosides） to fight the drug resistance of HSV.

A New Anticancer Drug

After some six years of hard work, a research team headed by Prof. Liu Zhivu (Z.Y. Liu) at the Shanghai Institute of Organic Chemistry, CAS, has scored major progress in independently generating a novel cancer killer called epothilone. Their findings have been granted three patents, and their research paper Total Synthesis of Epothilone: A Thorough Stereospecific Expoxidation of the 3-0-(4-methoxy) Benzyl Ether of Epothilone C has been accepted for publication in the Chemistry - European Journal.

新药研究与开发课程思政教学探索

在新药研究与开发课程教学中融入课程思政理念,将其与学科教学内容融合,发挥思政课程与课程思政的协同效应,是以专业技能知识为载体开展育人工作的必由之路。这一教学改革可有效推进以创新为核心的学生综合能力培养,是成功实现“健康中国”战略下复合型药学人才培养的有效途径。

医疗机构基于“三结合”中药新药研发及管理体系的构建

目的:在中药审评审批制度改革的政策背景下,围绕医疗机构,探索中医药理论、人用经验和临床试验相结合(简称“三结合”)的审评证据体系落地举措,为医疗机构中药制剂及中药新药研发提供参考。方法:根据“三结合”审评证据体系下中药新药研发的相关要求,从机构层面加强人用经验研究相关配套建设,从管理层面搭建中药研发、成果转化服务平台,从临床层面规范开展人用经验研究,构建医疗机构中药新药研发及管理体系。结果:医疗机构中药新药研发及管理体系的构建,有助于将临床诊疗数据转变为支持中药新药注册的人用经验证据,通过提高中药研发水平促进中药新药转化。结论:在医疗机构构建基于“三结合”的中药新药研发及管理体系,是“三结合”审评证据体系落地、政策引导研发实践的路径之一。

同质化教学条件下参与科研创新实践对临床药学专业本科生新药研究与开发课程成绩的影响

大学生参与科研创新实践是高校人才培养的重要环节。本文收集某高校临床药学专业本科生参与科研创新实践的信息,分析同质化教学条件下参加科研创新实践对其在新药研究与开发课程中成绩的影响。结果表明,参加科研创新实践可以有效提升临床药学专业本科生新药研究与开发课程成绩,提高其对基本概念的理解能力和科研实验设计能力。

改良型左甲状腺素钠相关药疹2例

优甲乐是一种人工合成外源性左甲状腺素,成分类似于甲状腺自然分泌的四碘甲状腺原氨酸,且可在外周器官中转化为游离三碘甲状腺原氨酸,并进一步结合受体,调节甲状腺功能。我院2例患者均为年轻女性,既往无药物及食物过敏史,也无家族遗传史。入院后行甲状腺切除术,术后常规给予优甲乐预防甲状腺肿复发,且服用同一批次、同一厂家优甲乐。2例患者前后出现不同程度的药物性皮疹,经抗过敏治疗后好转。2例患者的不良反应均与优甲乐的服用具有时间相关性,考虑为优甲乐的新辅料甘露醇引起。甘露醇静滴时,常见的不良反应包括过敏性皮疹和荨麻疹。本研究基于我院2例优甲乐疑似引起药物性皮疹病例,综合分析患者相关指标变化,并结合国内外相近案例回顾分析,探讨药物性皮疹特点及可能机制,以期提高临床医师对这一现象的关注,并为该疾病的深入研究、促进优甲乐安全合理用药提供一定参考。

药物化学专业研究生培养的实践与思考

本文根据笔者多年的科研及研究生指导经验,分析了药物化学研究生培养中存在的问题,总结了药物化学专业研究生培养的有效做法。