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Improving access to domestic innovative medicines: characteristics and trends of approved drugs in China 2010–2024 提高国产创新药的可及性：2010-2024 年中国获批药品的特点和趋势》。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-13 DOI: 10.1016/j.drudis.2024.104240
Yipeng Lan , Xiaofeng Lin , Yanmei Rao , Zhe Huang
{"title":"Improving access to domestic innovative medicines: characteristics and trends of approved drugs in China 2010–2024","authors":"Yipeng Lan ,&nbsp;Xiaofeng Lin ,&nbsp;Yanmei Rao ,&nbsp;Zhe Huang","doi":"10.1016/j.drudis.2024.104240","DOIUrl":"10.1016/j.drudis.2024.104240","url":null,"abstract":"<div><div>China has initiated drug regulatory reforms since 2015. Here, we analyze the characteristics and trends of domestic innovative drugs approved for marketing in China from January 2010 to May 2024 to explore the effectiveness of drug regulatory reform. Overall, 219 drugs were approved, with growth in chemicals and therapeutic biologics post-reform. Single-arm trials as an important option for clinical trial design of antineoplastic agents increased. The time for each link from investigational new drug (IND) to new drug application (NDA) has been shortened post-reform. Moreover, the time for access to medical insurance for approved drugs has been shortened and price reductions have been increased. China’s drug regulatory reforms have made progress in improving the accessibility of domestic innovative drugs.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104240"},"PeriodicalIF":6.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antibody–drug conjugates: prospects for the next generation 抗体-药物共轭物：下一代产品的前景。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-13 DOI: 10.1016/j.drudis.2024.104241
Meriem Grairi , Marc Le Borgne
{"title":"Antibody–drug conjugates: prospects for the next generation","authors":"Meriem Grairi ,&nbsp;Marc Le Borgne","doi":"10.1016/j.drudis.2024.104241","DOIUrl":"10.1016/j.drudis.2024.104241","url":null,"abstract":"<div><div>The concept of a ‘magic bullet’ was first introduced by Paul Ehrlich in the early 1900s, he foresaw the advent of targeted therapies and the specific killing of harmful cells and/or microorganisms. However, these therapies were only used in the clinic after the second half of the 20th century with the development of specific monoclonal antibodies. To date, 13 antibody–drug conjugates (ADCs) are commercially available. Many advances have been made by modifying one or several of the three main components of an ADC, namely the antibody, the cleavable or non-cleavable linker or the payload, and by integrating conjugation chemistry. Despite these efforts, some problems have emerged and thus limit their effectiveness. New strategies could overcome these problems and identify the next generation of ADC.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104241"},"PeriodicalIF":6.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond CL and VSS: A comprehensive approach to human pharmacokinetic predictions 超越 CL 和 VSS：人体药代动力学预测的综合方法。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-08 DOI: 10.1016/j.drudis.2024.104238
Anneke Himstedt , Hermann Rapp , Peter Stopfer , Ralf Lotz , Stefan Scheuerer , Thomas Arnhold , Achim Sauer , Jens Markus Borghardt
{"title":"Beyond CL and VSS: A comprehensive approach to human pharmacokinetic predictions","authors":"Anneke Himstedt ,&nbsp;Hermann Rapp ,&nbsp;Peter Stopfer ,&nbsp;Ralf Lotz ,&nbsp;Stefan Scheuerer ,&nbsp;Thomas Arnhold ,&nbsp;Achim Sauer ,&nbsp;Jens Markus Borghardt","doi":"10.1016/j.drudis.2024.104238","DOIUrl":"10.1016/j.drudis.2024.104238","url":null,"abstract":"<div><div>This article presents a comprehensive examination of processes related to the prediction of human pharmacokinetics (PK), a crucial task of clinical drug candidate selection. By systematically incorporating <em>in vitro</em> absorption, distribution, metabolism and excretion (ADME) and <em>in vivo</em> PK data with expert judgement, the study achieves high-quality human PK predictions for 40 orally administered compounds from Boehringer Ingelheim’s new chemical entity (NCE) portfolio. Overall, the article provides a detailed evaluation of and guidance for a structured process to predict full concentration–time profiles beyond single-parameter predictions, using state-of-the-art methodologies. Furthermore, it discusses future challenges and improvements, and aims to provide valuable insights for scientists working in drug metabolism and PK (DMPK) or PK/pharmacodynamics (PK/PD) modelling.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104238"},"PeriodicalIF":6.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immune safety challenges facing the preclinical assessment and clinical progression of cell therapies 细胞疗法的临床前评估和临床进展所面临的免疫安全性挑战。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-08 DOI: 10.1016/j.drudis.2024.104239
Stephanie M. Bates , Kelly V. Evans , Louise Delsing , Ryan Wong , Georgina Cornish , Mahnoush Bahjat
{"title":"Immune safety challenges facing the preclinical assessment and clinical progression of cell therapies","authors":"Stephanie M. Bates ,&nbsp;Kelly V. Evans ,&nbsp;Louise Delsing ,&nbsp;Ryan Wong ,&nbsp;Georgina Cornish ,&nbsp;Mahnoush Bahjat","doi":"10.1016/j.drudis.2024.104239","DOIUrl":"10.1016/j.drudis.2024.104239","url":null,"abstract":"<div><div>The promise of curative outcomes for life-limiting diseases using cell therapies is starting to become a reality, not only for patients with end-stage cancer, but also increasingly for regenerative therapies, including dentistry, ocular, neurodegenerative, and cardiac diseases. The introduction of often genetically modified cells into a patient can come with an extensive range of safety considerations. From an immune perspective, cell-based therapies carry inherent consequences and consideration of factors, such as the cell source (donor-derived autologous cells versus allogeneic cells), the intrinsic cellular nature of the therapy, and engineering/manufacturing methods, all of which influence the likelihood of inducing unwanted immune responses. Here, we provide an overview of the potential immune safety risks associated with cell therapies and explore possible mitigation approaches.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104239"},"PeriodicalIF":6.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Revisiting the GBB reaction and redefining its relevance in medicinal chemistry: A review 重新审视 GBB 反应并重新定义其在药物化学中的相关性：综述。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-08 DOI: 10.1016/j.drudis.2024.104237
Pratibha Shukla , Chandra Sourabh Azad , Deepa Deswal , Anudeep Kumar Narula
{"title":"Revisiting the GBB reaction and redefining its relevance in medicinal chemistry: A review","authors":"Pratibha Shukla ,&nbsp;Chandra Sourabh Azad ,&nbsp;Deepa Deswal ,&nbsp;Anudeep Kumar Narula","doi":"10.1016/j.drudis.2024.104237","DOIUrl":"10.1016/j.drudis.2024.104237","url":null,"abstract":"<div><div>Multicomponent reactions (MCRs) have significant relevance in the field of synthetic chemistry, and in recent times one of the MCR variants, named the Groebke–Blackburn–Bienaymé (GBB) reaction, has attracted massive attention for the synthesis of biologically important scaffolds. The present review elaborates on the chemical advancement reported for the GBB reaction with an emphasis on the role of various catalytic systems. Further, the role of the GBB reaction has been redefined as a standard protocol for the synthesis of an array of potential bioactive compounds.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104237"},"PeriodicalIF":6.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The global status of bioequivalence trials: a comprehensive clinical trial landscape analysis based on the Trialtrove database 生物等效性试验的全球现状：基于 Trialtrove 数据库的临床试验综合分析。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-07 DOI: 10.1016/j.drudis.2024.104223
Xiuxin Zhong , Shaojing Lin , Mingxia Deng , Ling Guan
{"title":"The global status of bioequivalence trials: a comprehensive clinical trial landscape analysis based on the Trialtrove database","authors":"Xiuxin Zhong ,&nbsp;Shaojing Lin ,&nbsp;Mingxia Deng ,&nbsp;Ling Guan","doi":"10.1016/j.drudis.2024.104223","DOIUrl":"10.1016/j.drudis.2024.104223","url":null,"abstract":"<div><div>This study presents a comprehensive analysis of the global bioequivalence (BE) trial landscape over the past 21 years, utilizing data from the Trialtrove database. We analyzed 12,450 BE trials conducted from 2003 to 2023, revealing a significant upward trend in trial numbers. Among the analysis, the primary therapeutic areas identified were cardiovascular diseases (23.17%) and metabolic/endocrinology conditions (18.91%). China leads in BE trials, accounting for 57.20% of the total, followed by Russia and the United States. Most trials are sponsored by the industry, predominantly by generic pharmaceutical companies. This study highlights the importance of diverse representation in trial populations to enhance the validity of results. We discuss strategies for improving trial success rates, including preliminary trials and in vitro dissolution testing. Furthermore, the need for international harmonization of generic drug standards is emphasized, along with the potential impact of advanced technologies, such as artificial intelligence, on future BE research.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104223"},"PeriodicalIF":6.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharma innovation: how evolutionary economics is shaping the future of pharma R&D 医药创新：进化经济学如何塑造医药研发的未来。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-06 DOI: 10.1016/j.drudis.2024.104222
Alexander Schuhmacher
{"title":"Pharma innovation: how evolutionary economics is shaping the future of pharma R&D","authors":"Alexander Schuhmacher","doi":"10.1016/j.drudis.2024.104222","DOIUrl":"10.1016/j.drudis.2024.104222","url":null,"abstract":"<div><div>This paper describes the theory of evolutionary economics in the context of pharmaceutical R&amp;D. In this context, the R&amp;D productivity crisis acts as a key selection mechanism, and R&amp;D, technology and industry trends provide mechanisms of variation. Drawing on today’s prevailing business model among leading pharmaceutical companies, the biotech-leveraged pharma company (BIPCO), I propose two new value creation logics: the technology-investigating pharma company (TIPCO) and the asset-integrating pharma company (AIPCO). Although some companies already share aspects of these business models, it is not yet clear, in terms of evolutionary economics, what the ultimate outcome of the evolutionary process in pharma R&amp;D will be.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104222"},"PeriodicalIF":6.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Contents page 目录页
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-01 DOI: 10.1016/S1359-6446(24)00356-8
{"title":"Contents page","authors":"","doi":"10.1016/S1359-6446(24)00356-8","DOIUrl":"10.1016/S1359-6446(24)00356-8","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104231"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142661282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in molecular glues: exploring chemical space and design principles for targeted protein degradation 分子胶的进展：探索定向降解蛋白质的化学空间和设计原则。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-01 DOI: 10.1016/j.drudis.2024.104205
Hemant Kumar S , Muthukumaran Venkatachalapathy , Ramesh Sistla , Vasanthanathan Poongavanam
{"title":"Advances in molecular glues: exploring chemical space and design principles for targeted protein degradation","authors":"Hemant Kumar S ,&nbsp;Muthukumaran Venkatachalapathy ,&nbsp;Ramesh Sistla ,&nbsp;Vasanthanathan Poongavanam","doi":"10.1016/j.drudis.2024.104205","DOIUrl":"10.1016/j.drudis.2024.104205","url":null,"abstract":"<div><div>The discovery of the E3 ligase cereblon (CRBN) as the target of thalidomide and its analogs revolutionized the field of targeted protein degradation (TPD). This ubiquitin-mediated degradation pathway was first harnessed by bivalent degraders. Recently, the emergence of low-molecular-weight molecular glue degraders (MGDs) has expanded the TPD landscape, because MGDs operate via the same mechanism while offering attractive physicochemical properties that are consistent with small-molecule therapeutics. This review delves into the discovery and advancement of MGDs, with case studies on cyclin K and the zinc finger protein IKZF2, highlighting the design principles, biological assays and therapeutic applications. Additionally, it examines the chemical space of molecular glues and outlines the collaborative efforts that are fueling innovation in this field.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104205"},"PeriodicalIF":6.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive analysis of acetylcholinesterase inhibitor and reactivator complexes: implications for drug design and antidote development 乙酰胆碱酯酶抑制剂和再激活剂复合物的综合分析：对药物设计和解毒剂开发的影响。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-29 DOI: 10.1016/j.drudis.2024.104217
Weronika Bagrowska, Angelika Karasewicz, Artur Góra
{"title":"Comprehensive analysis of acetylcholinesterase inhibitor and reactivator complexes: implications for drug design and antidote development","authors":"Weronika Bagrowska,&nbsp;Angelika Karasewicz,&nbsp;Artur Góra","doi":"10.1016/j.drudis.2024.104217","DOIUrl":"10.1016/j.drudis.2024.104217","url":null,"abstract":"<div><div>The main function of acetylcholinesterase (AChE) is to regulate the levels of one of the most important neurotransmitters: acetylcholine. This makes AChE an ideal molecular target for the treatment of neurodegenerative diseases and dementia (such as Alzheimer’s disease), as well as for the neutralisation of natural toxins (e.g., venom peptides) and chemical warfare agents. The significance of AChE inhibitors in slowing the progression of dementia, as well as the role of reactivators in treating poisoned individuals, is reflected in several co-crystallised complexes deposited in the Protein Data Bank. In this study, we analysed all deposited AChE–small-molecule complexes to gain insights into compound binding and to provide guidance for the future design of therapeutic drugs and new antidotes.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104217"},"PeriodicalIF":6.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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