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Efficacy and challenges involving combination therapies in CLL. 联合疗法在 CLL 中的疗效与挑战。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-15 DOI: 10.1016/j.drudis.2024.104243
Majed A Alanazi, Faith A A Kwa, Musab M A Omar, Juliana Antonipillai, Denise E Jackson
{"title":"Efficacy and challenges involving combination therapies in CLL.","authors":"Majed A Alanazi, Faith A A Kwa, Musab M A Omar, Juliana Antonipillai, Denise E Jackson","doi":"10.1016/j.drudis.2024.104243","DOIUrl":"https://doi.org/10.1016/j.drudis.2024.104243","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL), a malignant tumour, is characterized by expansion of mature monoclonal B lymphocytes expressing CD23 and CD5 in secondary lymphocytic organs, blood, and bone marrow. Here, we provide an in-depth review of CLL, emphasizing its pathophysiology, cytogenic changes, and treatment strategies, particularly the efficacy and challenges of treatments, such as Bruton tyrosine kinase (BTK) inhibitors, B cell lymphoma 2 (BCL2) inhibitors, and phosphatidylinositol 3-kinase (PI3K) inhibitors, as well as the need to understand their role in managing disease progression, chemoresistance, and intolerance. In addition, we explore efficacy based on patient response and comparison between monotherapy and combination therapy. We also highlight the need for innovative strategies to overcome treatment resistance and enhance patient outcomes.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104243"},"PeriodicalIF":6.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646063","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
Strategic partnerships for AI-driven drug discovery: The role of relational dynamics. 人工智能驱动药物发现的战略伙伴关系：关系动力学的作用。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-14 DOI: 10.1016/j.drudis.2024.104242
Stefan Kint, Wilfred Dolfsma, Douglas Robinson
{"title":"Strategic partnerships for AI-driven drug discovery: The role of relational dynamics.","authors":"Stefan Kint, Wilfred Dolfsma, Douglas Robinson","doi":"10.1016/j.drudis.2024.104242","DOIUrl":"10.1016/j.drudis.2024.104242","url":null,"abstract":"<p><p>Artificial intelligence-driven drug discovery (AIDD) companies hold significant promise for transforming pharmaceutical development, yet little is known about how they manage partnerships with established pharmaceutical firms. To address this research gap, our study explores how AIDD companies develop and leverage relational capabilities to enhance collaboration effectiveness. Through a case study approach, we focus on four key relational aspects: identifying complementary capabilities, establishing effective governance mechanisms, creating relationship-specific assets, and developing interfirm knowledge-sharing routines. Our findings demonstrate that particularly effective governance of intellectual property is essential for partnership success. We offer actionable recommendations for AIDD companies to strengthen collaborations, thereby contributing to the realization of AI's potential in drug discovery.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104242"},"PeriodicalIF":6.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637900","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
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, Xiaofeng Lin, Yanmei Rao, Zhe Huang","doi":"10.1016/j.drudis.2024.104240","DOIUrl":"10.1016/j.drudis.2024.104240","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"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, Marc Le Borgne","doi":"10.1016/j.drudis.2024.104241","DOIUrl":"10.1016/j.drudis.2024.104241","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"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":"","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 V<sub>SS</sub>: A comprehensive approach to human pharmacokinetic predictions.","authors":"Anneke Himstedt, Hermann Rapp, Peter Stopfer, Ralf Lotz, Stefan Scheuerer, Thomas Arnhold, Achim Sauer, Jens Markus Borghardt","doi":"10.1016/j.drudis.2024.104238","DOIUrl":"10.1016/j.drudis.2024.104238","url":null,"abstract":"<p><p>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 in vitro absorption, distribution, metabolism and excretion (ADME) and in vivo 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, PK and pharmacodynamics.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Highlighting roles of autophagy in human diseases: a perspective from single-cell RNA sequencing analyses. 突显自噬在人类疾病中的作用：单细胞 RNA 测序分析的视角。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-11-08 DOI: 10.1016/j.drudis.2024.104224
Anis Khalafiyan, Mahmood Fadaie, Fatemeh Khara, Ali Zarrabi, Fariborz Moghadam, Hossein Khanahmad, Marco Cordani, Maryam Boshtam
{"title":"Highlighting roles of autophagy in human diseases: a perspective from single-cell RNA sequencing analyses.","authors":"Anis Khalafiyan, Mahmood Fadaie, Fatemeh Khara, Ali Zarrabi, Fariborz Moghadam, Hossein Khanahmad, Marco Cordani, Maryam Boshtam","doi":"10.1016/j.drudis.2024.104224","DOIUrl":"10.1016/j.drudis.2024.104224","url":null,"abstract":"<p><p>Autophagy, the lysosome-driven breakdown of intracellular components, is pivotal in regulating eukaryotic cellular processes and maintaining homeostasis, making it physiologically important even under normal conditions. Cellular mechanisms that involve autophagy include the starvation response, intracellular quality control, early development, and cell differentiation. Despite its established health significance, the role of autophagy in cancer and other diseases is unclear. It is important to understand this mechanism thoroughly so that innovative therapies against various diseases can be designed and implemented and so that drugs can be developed to protect human health. High-throughput technologies have allowed researchers to study transcriptional landscapes at single-cell resolution, improving our understanding of autophagy pathways in various physiological and pathological conditions. This paper discusses single-cell RNA sequencing advances in autophagy research and the molecular characterization of multiple diseases.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"104224"},"PeriodicalIF":6.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610826","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
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, Kelly V Evans, Louise Delsing, Ryan Wong, Georgina Cornish, Mahnoush Bahjat","doi":"10.1016/j.drudis.2024.104239","DOIUrl":"10.1016/j.drudis.2024.104239","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"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":"","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, Chandra Sourabh Azad, Deepa Deswal, Anudeep Kumar Narula","doi":"10.1016/j.drudis.2024.104237","DOIUrl":"10.1016/j.drudis.2024.104237","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":" ","pages":"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
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
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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