International journal of drug discovery and pharmacology最新文献

{"title":"Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models","authors":"Yingjuan Liu, Honglin Xu, S. Abraham, X. Wang, B. Keavney","doi":"10.53941/ijddp.v1i1.188","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.188","url":null,"abstract":"Review\u0000Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models\u0000\u0000Yingjuan Liu *, Honglin Xu, Sabu Abraham, Xin Wang, and Bernard D. Keavney*\u0000\u0000\u0000Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, M13 9PT, UK.\u0000* Correspondence: yingjuan.liu@manchester.ac.uk (Yingjuan Liu);\u0000bernard.keavney@manchester.ac.uk (Bernard D. Keavney)\u0000 \u0000 \u0000Received: 1 November 2022\u0000Accepted: 24 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Currently, with an increased requirement for new therapeutic strategies, preclinical drug testing or screening platforms have rapidly evolved in recent years. In comparison to traditional 2D cell cultures, 3D organoids or spheroids with or without scaffolds improve the microenvironment of in vitro cultures, advancing the in vitro biological observation and enabling mechanistic studies of drug reactions in the human tissue-like environment. 3D organoids and spheroids are straightforward to produce, and relatively uniform in size and shape. This helps to facilitate high throughput screening requirements. Spheroids and organoids have been applied in anti-cancer drug testing, toxicity evaluations, as well as mechanism studies for variable organ systems, including the intestine, liver, pancreas, brain, and heart. Among 3D cultures of spheroids and organoids, ‘tumour spheroids’ formed by dissociated tumour tissues or cancer cell lines are relatively simple in composition and commonly applied to anticancer drug screening. The ‘healthy organoids’ differentiated from hiPSCs/hESCs are more complex in cell composition, distribution, structure and function with higher similarity to in vivo organs, and have found applications in toxicity tests, personalised medicine, and therapeutic and mechanistic studies. In most cases, the multicellular 3D organoids are more resistant and stable in reaction to stimulations or chemicals in vitro , suggesting more accurate modelling of in vivo responses. Here, we review recent progress in human-origin organoid/spheroid systems and their applications in preclinical studies.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"132 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83743757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances of the Target-Based and Phenotypic Screenings and Strategies in Drug Discovery","authors":"Shou-bao Wang, Zihan Wang, Lianhua Fang, Yang Lv, G. Du","doi":"10.53941/ijddp.v1i1.199","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.199","url":null,"abstract":"Review\u0000Advances of the Target-Based and Phenotypic Screenings and Strategies in Drug Discovery\u0000\u0000Shoubao Wang 1,*, Zihan Wang1, Lianhua Fang1, Yang Lv2, and Guanhua Du1,*\u0000\u0000\u00001 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.\u00002 Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.\u0000* Correspondence: shoubaowang@imm.ac.cn (Shoubao Wang); dugh@imm.ac.cn (Guanhua Du).\u0000 \u0000 \u0000Received: 8 November 2022\u0000Accepted: 15 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Drug discovery and development is a complex and expensive process. There are two approaches, phenotypic and target-based approaches, each holding different advantages for screening novel drug candidates when pursuing successful marketing authorization. However, the attrition rates of drug candidates continue to increase. In this review, we discuss recent successes and ongoing advances in phenotypic screening and target-based screening for drug discovery. We also explore how strategic and technological innovations may fuel new approaches in drug discovery. There are two approaches in drug discovery.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82225834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Bench to Bedside: Current Developments in RNA-Based Therapies for Treatment of Hyperlipidemia","authors":"Yufei Zhou, Chen Chen","doi":"10.53941/ijddp.v1i1.141","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.141","url":null,"abstract":"Review\u0000From Bench to Bedside: Current Developments in RNA-Based Therapies for Treatment of Hyperlipidemia\u0000\u0000Yufei Zhou and Chen Chen *\u0000\u0000\u0000Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.\u0000* Correspondence: chenchen@tjh.tjmu.edu.cn; Tel. & Fax: 86-27-6937-8422.\u0000 \u0000 \u0000Received: 7 October 2022\u0000Accepted: 1 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Hyperlipidemia is one of the conditions that constitute metabolic disorder and it is a common public health problem. The condition is characterized by increased levels of cholesterol, triglycerides and/or lipoproteins; it is a recognized as a risk factor for the onset of many diseases such as type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. Up to now, the primary drugs for treating hyperlipidemia are statins and monoclonal antibody drugs against proprotein convertase subtilisin/kexin type 9 (PCSK9). The main limitation of statins for long-term use is intolerable side effects. Evolocumab and Alirocumab, two monoclonal antibodies against PCSK9, can effectively decrease the level of low-density lipoprotein cholesterol (LDL-C) in patients with statin intolerance and familial hypercholesterolemia, while causing fewer side effects. However, due to its short half-life and high costs, these monoclonal antibody treatments might result in patients’ non-compliance with medication and considerable economic burden on patients. Given that RNA plays a key role in gene regulation, RNA-based therapeutics have become powerful blueprints for designing new anti-hyperlipidemia drugs. Here, we summarized RNA-based therapeutic strategies and the current clinical trials for RNA drugs in hyperlipidemia treatment.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81076074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}