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Targeting FLT3 for treating diseases: FLT3 inhibitors 靶向FLT3治疗疾病：FLT3抑制剂
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-05-01 DOI: 10.1016/j.drudis.2025.104367
Qing-Yun Rong , Yu Lu , Wen Zhang , Guo-Wu Rao , Quan Zheng
{"title":"Targeting FLT3 for treating diseases: FLT3 inhibitors","authors":"Qing-Yun Rong ,&nbsp;Yu Lu ,&nbsp;Wen Zhang ,&nbsp;Guo-Wu Rao ,&nbsp;Quan Zheng","doi":"10.1016/j.drudis.2025.104367","DOIUrl":"10.1016/j.drudis.2025.104367","url":null,"abstract":"<div><div>FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase (RTK) expressed mainly in hematopoietic stem and progenitor cells and often mutated in hematological tumors, such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). A variety of FLT3 inhibitors have been approved and adopted for the treatment of AML. However, these suffer resistance problems, and further studies are needed. Here, we review the current status of research on FLT3 inhibitors in AML, discuss the occurrence of resistance, and suggest approaches to overcome such resistance.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104367"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907728","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
An overview of progress in human metapneumovirus (hMPV) research: Structure, function, and therapeutic opportunities 人偏肺病毒（hMPV）研究进展综述：结构、功能和治疗机会
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-05-01 DOI: 10.1016/j.drudis.2025.104364
Nadine Krüger , Stefan A. Laufer , Thanigaimalai Pillaiyar
{"title":"An overview of progress in human metapneumovirus (hMPV) research: Structure, function, and therapeutic opportunities","authors":"Nadine Krüger ,&nbsp;Stefan A. Laufer ,&nbsp;Thanigaimalai Pillaiyar","doi":"10.1016/j.drudis.2025.104364","DOIUrl":"10.1016/j.drudis.2025.104364","url":null,"abstract":"<div><div>The human metapneumovirus (hMPV), a member of the Pneumoviridae family, is a significant respiratory pathogen that causes severe infections in infants, children, the elderly, adults with chronic illnesses, and individuals with immunocompromised conditions. Globally, hMPV is recognized as the second leading cause of bronchiolitis and pneumonia among children under five. The absence of targeted antiviral treatments or vaccines for hMPV significantly strains the global health-care system. This review summarizes recent advances and scientific findings on hMPV by reviewing the current literature on its life cycle, structure, function, prevention, and treatment options.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104364"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907726","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
Leveraging mHealth wearables for managing patients with Alzheimer’s disease: a scoping review 利用移动健康可穿戴设备管理阿尔茨海默病患者：范围审查
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-05-01 DOI: 10.1016/j.drudis.2025.104363
Kenta Noda , Itsuki Kageyama , Yoshiyuki Kobayashi , Yeongjoo Lim , Shintaro Sengoku , Kota Kodama
{"title":"Leveraging mHealth wearables for managing patients with Alzheimer’s disease: a scoping review","authors":"Kenta Noda ,&nbsp;Itsuki Kageyama ,&nbsp;Yoshiyuki Kobayashi ,&nbsp;Yeongjoo Lim ,&nbsp;Shintaro Sengoku ,&nbsp;Kota Kodama","doi":"10.1016/j.drudis.2025.104363","DOIUrl":"10.1016/j.drudis.2025.104363","url":null,"abstract":"<div><div>In this scoping review, we examine the role of wearable devices in diagnosing, treating, and monitoring Alzheimer’s disease (AD) and mild cognitive impairment (MCI). It identifies various devices, including fitness trackers, smartwatches, electroencephalographic equipment, and sensors, which are used for monitoring physical activity, sleep patterns, and cognitive functions. Our review highlights the potential of these devices for early diagnosis and treatment, improving patient autonomy and quality of life. However, challenges, such as data privacy, device adherence, and technical limitations, remain. Future research should focus on integrating wearable devices with advanced diagnostic tools and validating their effectiveness across diverse populations.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104363"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886436","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
A cutting-edge solution to a Gordian knot? Aptamers targeting cancer stem cell markers for strategic cancer therapy 高尔迪结的尖端解决方案？靶向癌症干细胞标记的适体用于战略性癌症治疗
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-05-01 DOI: 10.1016/j.drudis.2025.104365
Aneesa Muzaffar , Asilah Ahmad Tajudin , Amir Syahir
{"title":"A cutting-edge solution to a Gordian knot? Aptamers targeting cancer stem cell markers for strategic cancer therapy","authors":"Aneesa Muzaffar ,&nbsp;Asilah Ahmad Tajudin ,&nbsp;Amir Syahir","doi":"10.1016/j.drudis.2025.104365","DOIUrl":"10.1016/j.drudis.2025.104365","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) are key drivers of tumor proliferation and serve as a basis for therapeutic resistance, metastasis, and recurrence. The erratic efficacy of conventional therapeutic approaches is limited because of their inability to exterminate CSCs. This has spurred the development of novel cancer treatment paradigms that target specifically these cells. Importantly, CSCs are identified and classified based on the differential expression of biomarkers, facilitating their precise isolation and tailored therapeutic interventions. Numerous promising approaches have been developed to target CSC markers, paving the way to precision medicine in cancer treatment. Aptamers are molecularly targeting agents comprising single-strand oligonucleotides arranged in a unique fashion that allows them to bind their targets, including cancer biomarkers, with high specificity and affinity. Given their programmable nature, they can be chemically modified and integrated with various diagnostic components, including nanoparticles (NPs), drugs, and therapeutic RNAs, thereby enhancing their applicability in disease treatment. In this review, we shed light on various aptamer designs that show potential to target putative CSC markers and to efficiently deliver therapeutic moieties.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104365"},"PeriodicalIF":6.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907727","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
Artificial intelligence in preclinical research: enhancing digital twins and organ-on-chip to reduce animal testing 临床前研究中的人工智能：增强数字双胞胎和器官芯片以减少动物实验
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-04-17 DOI: 10.1016/j.drudis.2025.104360
Amit Gangwal , Antonio Lavecchia
{"title":"Artificial intelligence in preclinical research: enhancing digital twins and organ-on-chip to reduce animal testing","authors":"Amit Gangwal ,&nbsp;Antonio Lavecchia","doi":"10.1016/j.drudis.2025.104360","DOIUrl":"10.1016/j.drudis.2025.104360","url":null,"abstract":"<div><div>Artificial intelligence (AI) is reshaping preclinical drug research offering innovative alternatives to traditional animal testing. Advanced techniques, including machine learning (ML), deep learning (DL), AI-powered digital twins (DTs), and AI-enhanced organ-on-a-chip (OoC) platforms, enable precise simulations of complex biological systems. AI plays a critical role in overcoming the limitations of DTs and OoC, improving their predictive power and scalability. These technologies facilitate early-stage, reliable evaluations of drug safety and efficacy, addressing ethical concerns, reducing costs, and accelerating drug development while adhering to the 3Rs principle (Replace, Reduce, Refine). By integrating AI with these advanced models, preclinical research can achieve greater accuracy and efficiency in drug discovery. This review examines the transformative impact of AI in preclinical research, highlighting its advancements, challenges, and the critical steps needed to establish AI as a cornerstone of ethical and efficient drug discovery.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104360"},"PeriodicalIF":6.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878374","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 artificial intelligence-envisioned technologies for protein and nucleic acid research 人工智能技术在蛋白质和核酸研究中的进展
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-04-17 DOI: 10.1016/j.drudis.2025.104362
Amol D. Gholap , Abdelwahab Omri
{"title":"Advances in artificial intelligence-envisioned technologies for protein and nucleic acid research","authors":"Amol D. Gholap ,&nbsp;Abdelwahab Omri","doi":"10.1016/j.drudis.2025.104362","DOIUrl":"10.1016/j.drudis.2025.104362","url":null,"abstract":"<div><div>Artificial intelligence (AI) and machine learning (ML) have revolutionized pharmaceutical research, particularly in protein and nucleic acid studies. This review summarizes the current status of AI and ML applications in the pharmaceutical sector, focusing on innovative tools, web servers, and databases. This paper highlights how these technologies address key challenges in drug development including high costs, lengthy timelines, and the complexity of biological systems. Furthermore, the potential of AI in personalized medicine, cancer drug response prediction, and biomarker identification is discussed. The integration of AI and ML in pharmaceutical research promises to accelerate drug discovery, reduce development costs, and ultimately lead to more effective and personalized therapeutic strategies.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104362"},"PeriodicalIF":6.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874573","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
Target & Mechanism Selection in Pharmaceutical Innovation: A Source for Concern or Optimism? 药物创新的目标与机制选择：值得关注还是值得乐观？
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-04-17 DOI: 10.1016/j.drudis.2025.104361
Michael S. Kinch, Zachary Kraft, Tyler Schwartz
{"title":"Target & Mechanism Selection in Pharmaceutical Innovation: A Source for Concern or Optimism?","authors":"Michael S. Kinch,&nbsp;Zachary Kraft,&nbsp;Tyler Schwartz","doi":"10.1016/j.drudis.2025.104361","DOIUrl":"10.1016/j.drudis.2025.104361","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104361"},"PeriodicalIF":6.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882864","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
Advancing ocular gene therapy: a machine learning approach to enhance delivery, uptake and gene expression 推进眼部基因治疗：一种增强传递、摄取和基因表达的机器学习方法
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-04-12 DOI: 10.1016/j.drudis.2025.104359
Sareh Aghajanpour , Hamid Amiriara , Pedram Ebrahimnejad , Roderick A. Slavcev
{"title":"Advancing ocular gene therapy: a machine learning approach to enhance delivery, uptake and gene expression","authors":"Sareh Aghajanpour ,&nbsp;Hamid Amiriara ,&nbsp;Pedram Ebrahimnejad ,&nbsp;Roderick A. Slavcev","doi":"10.1016/j.drudis.2025.104359","DOIUrl":"10.1016/j.drudis.2025.104359","url":null,"abstract":"<div><div>Ocular gene therapy offers a promising approach for treating various eye diseases, centered on the process of transfection, including delivery, cellular uptake and gene expression. This study addresses anatomical and physiological barriers, such as the eyelids, tear film, conjunctiva, cornea, sclera, choroid and retina, affecting therapeutic success. A three-step machine-learning approach is proposed. The first step predicts gene delivery efficacy by integrating molecular characteristics of the ocular gene therapy product, ocular barrier properties and patient demographics. The second step predicts cellular uptake rates, analyzing product penetration and cellular interactions. The final step forecasts gene expression levels, considering factors like nucleic acid type and endosomal escape. An artificial neural network model is recommended to capture complex, nonlinear relationships, enhancing our understanding of therapeutic and biological interactions.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104359"},"PeriodicalIF":6.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874528","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
Evaluation of the implementation effectiveness of accelerated drug marketing registration procedures in China: lessons from the 2016–2024 regulatory review 中国药品加速上市注册程序实施效果评价：2016-2024年监管审查的经验教训
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-04-10 DOI: 10.1016/j.drudis.2025.104353
Yipeng Lan , Li Wang , Xiaofeng Lin , Yiqing Wu , Zhe Huang
{"title":"Evaluation of the implementation effectiveness of accelerated drug marketing registration procedures in China: lessons from the 2016–2024 regulatory review","authors":"Yipeng Lan ,&nbsp;Li Wang ,&nbsp;Xiaofeng Lin ,&nbsp;Yiqing Wu ,&nbsp;Zhe Huang","doi":"10.1016/j.drudis.2025.104353","DOIUrl":"10.1016/j.drudis.2025.104353","url":null,"abstract":"<div><div>China has implemented accelerated drug marketing registration procedures (ADMRPs) since 2016, including priority review and approval (PRA), conditional approval (CA), and breakthrough therapy drugs (BTDs). This study analyzed the characteristics of drugs approved by ADMRPs from 2016 to 2024 and explored the implementation effectiveness of these procedures. Overall, 922 drugs were approved for marketing through five ADMRPs (or procedure combinations): PRA (759, 82.3%), CA (12, 1.3%), CA + PRA (108, 11.7%), BTD + PRA (23, 2.5%), and BTD + CA + PRA (20, 2.2%). Drugs approved through the different procedures differed widely in terms of drug attributes and clinical uses, clinical trial design, and drug registration and marketing. Implementing ADMRPs has demonstrated excellent results in accelerating the development and marketing of clinically value-driven drugs.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104353"},"PeriodicalIF":6.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852350","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 spindle assembly checkpoint: Molecular mechanisms and kinase-targeted drug discovery 纺锤体组装检查点：分子机制和激酶靶向药物的发现
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-04-10 DOI: 10.1016/j.drudis.2025.104355
Inês Lima , Fernanda Borges , António Pombinho , Daniel Chavarria
{"title":"The spindle assembly checkpoint: Molecular mechanisms and kinase-targeted drug discovery","authors":"Inês Lima ,&nbsp;Fernanda Borges ,&nbsp;António Pombinho ,&nbsp;Daniel Chavarria","doi":"10.1016/j.drudis.2025.104355","DOIUrl":"10.1016/j.drudis.2025.104355","url":null,"abstract":"<div><div>The spindle assembly checkpoint (SAC) is a surveillance mechanism required for the fidelity of chromosome segregation, ensuring that anaphase is not initiated until all chromosomes are properly attached to the mitotic spindle. In cancer cells, SAC inactivation leads to aneuploidy beyond the cell’s adaptation, culminating in cell death. This review provides a concise overview of the SAC signaling process and properties. Recent drug discovery strategies to selectively target kinases, particularly Aurora B and monopolar spindle kinase (MPS1), aimed at developing innovative anticancer agents able to override SAC are also presented.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104355"},"PeriodicalIF":6.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847966","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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