An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

Antibacterial resistance is a global health threat that requires further concrete action on the part of all countries.In this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and developed.Although several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in China.In this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since 2019.Information was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other reviews.As of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and updated.Among them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in phase-1.Most of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial protein.Overall,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in China.Hopefully,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

Computer-assisted anti-AIDS drug development: cyclophilin B against the HIV-1 subtype A V3 loop

Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.

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.

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-

Reference of New Zealand’s Drug Shortage Management Measures

Objective To provide a scientific reference for China’s drug shortage and supply mechanism by conducting a specific study on New Zealand’s management measures for dealing with the shortage of drugs.Methods Through reviewing the official website of the New Zealand Pharmaceutical Management Agency(PHARMAC)and relevant literature,the specific measures to deal with drug supply and shortage in New Zealand were sorted out,and then some countermeasures were put forward for our domestic drug supply.Results and Conclusion PHARMAC worked closely with the pharmaceutical suppliers and signed contracts to maintain their relationship.A sound drug supply mechanism has been established to respond to various supply issues.At present,there are some problems in drug supply in China,such as the lack of timely publicity of shortage information,the lack of management team for supply,and the lack of alternative drug supply mechanism.China should learn from the PHARMAC to establish a supply contract management team to promote the transparency of drug shortage information and seek alternative drug supply actively.

Regulation of “Checkpoint Molecule” Sheds New Light on Anti-Cancer Drug Development

The rivalry between T cells and tumor cells somewhat mimics the scene of 'Tom and Jerry,' an animated series in which Tom (a house cat) rarely succeeds in catching Jerry (a mouse), mainly because of Jerry’s cleverness and cunning abilities. In a way, tumor cells are like Jerry, in terms of their crafty and sneaky features.

New Developments in Drug Therapy and Research of Cerebral Vasospasm

In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new agents available for treatment of cerebral vasospasm is expanding rapidly along with rapid advances in pharmacology and physiology that are uncovering the mechanisms of this disease. Although there are many publications for treatment of cerebral vaso-spasm, most are focusing on different aspects of vasospasm treatment and many have limited value due to insufficient quality. Moreover, the complexity of this, in many cases deleterious condition, is enormous and the information needed to understand drug effects is accordingly often not readily available in a single source. A number of pharmacological and medical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Current research efforts promise the eventual production of new medical therapies. At last, recommendations for the use of different treatment stages based on currently available clinical data are provided.

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.

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.

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-

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。

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。

不同新型降糖药在2型糖尿病患者中的心血管改善作用进展

2型糖尿病是导致心血管疾病死亡的重要原因之一,合理控制血糖,可降低心血管疾病的发生风险,改善心血管疾病患者的预后结局。传统降糖药仅能降低血糖,对大血管合并症影响较小,而新型降糖药在2型糖尿病患者降糖预后方面有着诸多优势,也取得了较好的临床效果。新型降糖药包括肠促胰素类药物、二肽基肽酶-4抑制剂、钠-葡萄糖协同转运蛋白2抑制剂、葡萄糖激酶激动剂、胰岛淀粉样物多肽类似物等。本文总结2型糖尿病合并心血管疾病的发病现状,探讨不同新型降糖药对2型糖尿病患者心血管保护作用,展望不同新型降糖药物未来应用方向。