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.

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.

Study on medication rules of Chinese herbs in the regulation of necroptosis based on network pharmacology and data mining

Objective:To analyze the basis and medication rules of Chinese herbs in the regulation of necroptosis.Methods:With the help of GeneCards,DrugBank,TTD,DisGeNET,OMIM database to collect the action targets of necroptosis,the TCMSP database to obtain the target‑related compounds and Chinese herbs,and the ADME criteria and Lipinski rule as the conditions for screening,to build the target‑compound,target‑compound‑Chinese herbs network.The information of Chinese herbal medicine's sexual taste and meridian was collected,and the drug use pattern was analyzed.The information on the property,flavor and channel tropism of Chinese herbs was collected to analyze the medication laws.Molecular docking of core targets and compounds in the network with AutoDockTools software,and PyMOL software was used to display the combinations with good docking results.Results:A total of 12 potential targets acting on necroptosis were obtained,matching to 191 candidate compounds and 366 herbal medicines.Quercetin,wogonin,triptolide,licochalcone a,ellipticine are more important and may be the main small molecule substances underlying the regulation of necroptosis.The more important Chinese herbs are Licorice,Forsythia,Salivae Miltiorrhizae,Ginkgo Leaf,Eucommia ulmoides Oliv,etc.The herbal medicines are mainly bitter and pungent,with cold and warm taste,which were attributed to the liver and lung meridians.BCL2‑beta‑sitosterol、MAPK14‑luteolin、MAPK14‑formononetin、TP53‑formononetin are better molecular docking results,which have strong docking activity.Conclusion:The study systematically analyzes the material basis of regulating necroptosis and summarizes the general rule of regulating necroptosis in Chinese medicine,which provides ideas for clinical development of agents to interfere with necroptosis.

Analysis of Strategy for Extending Patent Protection of Rucaparib

As a knowledge-intensive and promising strategic emerging industry, the biomedical industry has high entry thresholds, large R&D investment, long cycle, high risk and high return. In all technical fields, the biomedical industry has the highest dependence on intellectual property rights, and the protection of pharmaceutical intellectual property rights by domestic and foreign biomedical enterprises also runs through the whole process of drug research and development. Extending the patent protection period of drugs as well as forming and strengthening patent fortresses requires a patent network that surrounds drugs to maximize the value of intellectual property protection, which is also the focus of every pharmaceutical company with patent rights. By analyzing the patent portfolio of Clovis Oncology Company in the United States on Rucaparib and the patent portfolio of other companies or applicants on Rucaparib, we can have a clearer understanding of the strategy of extending the patent protection period of a new drug product.

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.

Network pharmacology-based elucidation of molecular biological mechanisms of Qizhu Yuling Decoction for treatment of esophagus cancer

Objective:To investigate the active compounds,key targets and molecular mechanism of Qizhu Yuling Decoction in the treatment of esophageal carcinoma based on network pharmacology.Methods:The active compounds of Qizhu Yuling Decoction with anti-esophageal cancer activity were screened by TCMSP and literature search,and the drug targets were searched by DrugBank and predicted by SwissTargetPrediction.The esophageal cancer-related genes were obtained from GeneCards,OMIM,DrugBank,TTD,DisGeNET,and the intersection network was selected to obtain candidate genes.The"herb-compound-target-disease"network was constructed with Cytoscape,the PPI network was constructed in STRING and core network modules were screened.Gene ontology and KEGG enrichment analysis was performed by using Metascape,and the"pathway-gene"network was constructed to further screen key targets.Results:A total of 47 active compounds(19 Astragalus,4 Zedoary turmeric,11 Atractylodes macrocephala,9 Curcuma longa,5 Clematis root,and 5 Salvia chinensis),297 candidate genes,2413 GO and 119 KEGG pathways were obtained.Conclusion:The active compounds of Qizhu Yuling Decoction in the treatment of esophageal cancer are quercetin,kaempferol,glycine and ursolic acid.The potential targets are AKT1,MAPK1,MAPK3,PIK3R1 and RELA.GO involves oxidative stress,cell cycle,apoptosis and cell death,and KEGG involves typical cancer pathways,MAPK,NF-κB and PI3K-Akt signaling pathways.This study reveals the molecular biological mechanism of Qizhu Yuling Decoction in the treatment of esophageal cancer,and speculates that the function of potential targets focuses on the interaction of multiple signaling pathways,which can antagonize the proliferation,invasion,metastasis and recurrence of esophageal cancer and improve the prognosis of patients.This study provides new evidence for subsequent new drug development,clinical application and experimental study.

A Review on the Research of Precision Medicine for Cancer Based on the Integration of Traditional Chinese and Western Medicine

Objective:To summarize and expound the general situation of precision medicine for cancer according to the current international research hot spots and treatment frontiers of cancer.Methods:This article makes an inventory from five aspects of treatment methods,detection technology,new drug research and development,information data and traditional Chinese medicine,"from point to surface","from outside to inside"and"integration of Chinese and Western medicine",to explore the whole picture of tumor treatment and research.Results:With the rapid development of tumor precision medicine in recent years,the tumor treatment methods have been developed from single to multiple.The research technology has been changed from macro to micro.The therapeutic drugs have been changed from systemic chemotherapy to targeted therapy,immunotherapy and other technologies.The treatment concept has been changed from local to overall.And the integrated treatment methods of traditional Chinese and Western medicine have brought a new chapter to tumor treatment.Conclusion:Through a series of new technologies,new methods and new concepts,tumor precision medicine promotes the treatment of tumors with integrated Chinese and Western medicine into a new chapter.

ETCM v2.0:An update with comprehensive resource and rich annotations for traditional Chinese medicine

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 Java Script-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.

新药生殖发育毒性安全性评价的仪器确认要点

围绕药品非临床研究质量管理规范(GLP)体系下生殖发育毒性评价所使用仪器确认展开讨论,提供开展仪器确认所需要的关键事项:根据研究目的,选取合适种属的实验动物;动物数量应满足统计学需求;准确选取实验受试物,购入标准品或阳性药物;确定实用性强、干扰因素少的确认方法;把握实验关键点、排除其他因素对确认的干扰;建立准确度高可重现性好的评价标准;根据实验室基本情况以及研究目的,在标准作业程序(SOP)中规定不同仪器确认所需要的周期。现有生殖毒性仪器确认规范性、标准化成为实验室管理的新难点,需要努力推进其标准化规范化进程。

药物安全性评价新技术和新方法研究进展

药物引发的安全性问题一直受到各国药品管理部门广泛而高度的重视,药物安全性评价技术和方法更是各国学者研究的热点。近年来,随着科学技术的不断发展,新的安全性评价技术和方法不断出现,包括肝脏、肾脏、心脏等靶器官毒性,发育和生殖毒性,遗传毒性和致癌性等方面的评价技术和方法。本文主要结合本中心近10年来的研究成果,对药物安全性评价新技术和新方法的研究进展进行了综述。