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Effects of PCSK9 inhibitors on cancer, diabetes, and cardiovascular diseases PCSK9抑制剂对癌症、糖尿病和心血管疾病的影响
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-03-01 DOI: 10.1016/j.drudis.2025.104316
Mojgan Nejabat , Farzin Hadizadeh , Wael Almahmeed , Amirhossein Sahebkar
{"title":"Effects of PCSK9 inhibitors on cancer, diabetes, and cardiovascular diseases","authors":"Mojgan Nejabat ,&nbsp;Farzin Hadizadeh ,&nbsp;Wael Almahmeed ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.drudis.2025.104316","DOIUrl":"10.1016/j.drudis.2025.104316","url":null,"abstract":"<div><div>Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have potential applications in cancer therapy and as cholesterol-lowering treatments. The impact of PCSK9 suppression on both tumor growth and metastasis, as well as the management of diabetes, has been demonstrated. PCSK9i can also enhance outcomes and reduce cardiovascular (CV) events in individuals with a history of such events. In this review, we provide insights into the pharmacology, safety, and impact of PCSK9i. We highlight cutting-edge investigations, the development of innovative PCSK9i-based products, and a more comprehensive understanding of the potential effects of these drugs on cancer, diabetes, and CV and cerebrovascular diseases.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 3","pages":"Article 104316"},"PeriodicalIF":6.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475908","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
Polysaccharides as therapeutic vehicles in pancreatic cancer 多糖作为胰腺癌的治疗载体。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-03-01 DOI: 10.1016/j.drudis.2025.104320
Seema Kumari , Sujatha Peela , Ganji Purnachandra Nagaraju , Mundla Srilatha
{"title":"Polysaccharides as therapeutic vehicles in pancreatic cancer","authors":"Seema Kumari ,&nbsp;Sujatha Peela ,&nbsp;Ganji Purnachandra Nagaraju ,&nbsp;Mundla Srilatha","doi":"10.1016/j.drudis.2025.104320","DOIUrl":"10.1016/j.drudis.2025.104320","url":null,"abstract":"<div><div>Pancreatic cancer (PC) is highly aggressive, with rising incidence and mortality rates. It has significant therapy obstacles due to the limited clinical options, late-stage identification, dense tumor microenvironment (TME), and resistance to therapy. Recent advances might improve treatment consequences in therapy strategies that target important TME components. Moreover, new polymeric drug delivery techniques based on polysaccharides such as polymeric micelles, liposomes, and nanoparticles enhance the solubility of drugs, drug stability, and tumor-specific targeting, which increase the chances of circumventing resistance and improving the efficacy of treatment. Preclinical research has suggested that by modulating the TME and enhancing the efficacy of chemotherapy, polysaccharide-based therapy, such as RP02-1 and DPLL-functionalized amylose, may help treat PC.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 3","pages":"Article 104320"},"PeriodicalIF":6.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536290","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
Recent advancements in colchicine derivatives: Exploring synthesis, activities, and nanoformulations for enhanced therapeutic efficacy 秋水仙碱衍生物的最新进展：探索合成、活性和纳米配方以增强治疗效果。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-02-11 DOI: 10.1016/j.drudis.2025.104312
Marialucia Rubicondo , Gianluca Ciardelli , Clara Mattu , Jack A. Tuszynski
{"title":"Recent advancements in colchicine derivatives: Exploring synthesis, activities, and nanoformulations for enhanced therapeutic efficacy","authors":"Marialucia Rubicondo ,&nbsp;Gianluca Ciardelli ,&nbsp;Clara Mattu ,&nbsp;Jack A. Tuszynski","doi":"10.1016/j.drudis.2025.104312","DOIUrl":"10.1016/j.drudis.2025.104312","url":null,"abstract":"<div><div>The multifaceted anti-cancer properties of colchicine make it a promising candidate for tumor treatment. However, its application has been limited by poor solubility, low bioavailability, and systemic toxicity. Considerable efforts have been directed toward the development of colchicine derivatives and nanoformulations to overcome these challenges. In this review, we provide a comprehensive overview of recent advances in colchicine derivatives and nanoformulations for cancer treatment. Synthesis methods and <em>in vitro</em> antiproliferative assays for the reviewed derivatives and formulations are explored. Challenges, such as drug resistance and formulation optimization, are also addressed, along with future perspectives for leveraging the full potential of colchicine derivatives and their nanoformulations as innovative anti-cancer strategies, toward successful clinical applications.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 3","pages":"Article 104312"},"PeriodicalIF":6.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412562","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 fusion? Don’t buy your alliances partners if the goal is breakthrough innovation 制药公司融合?如果你的目标是突破性的创新，不要购买你的联盟伙伴。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-02-06 DOI: 10.1016/j.drudis.2025.104310
Killian McCarthy , Rick Aalbers
{"title":"Pharma fusion? Don’t buy your alliances partners if the goal is breakthrough innovation","authors":"Killian McCarthy ,&nbsp;Rick Aalbers","doi":"10.1016/j.drudis.2025.104310","DOIUrl":"10.1016/j.drudis.2025.104310","url":null,"abstract":"<div><div>This paper examines the innovation impact of acquiring alliance partners. We argue that although pre-acquisition alliances might aid post-acquisition integration efforts, by offering insights into targets’ proprietary technologies, the familiarity that they foster will also significantly influence the firms post-acquisition innovation outcomes. We tested this using a dataset involving 252 firms, 2398 acquisitions, and 125,440 patents. We found that acquisitions involving former alliance partners increased innovation output. We also found that they fostered the development of more exploitative innovation. However, we found that these transitions inhibit the development of breakthrough innovation by limiting the firm’s exposure to novel insights. We conclude, therefore, that alliance partner acquisitions are far from an innovation panacea for the pharm industry.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 3","pages":"Article 104310"},"PeriodicalIF":6.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373501","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
Death ligand receptor (DLR) signaling: Its non-apoptotic functions in cancer and the consequences of DLR-directed therapies 死亡配体受体（DLR）信号：其在癌症中的非凋亡功能和DLR定向治疗的后果。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-02-01 DOI: 10.1016/j.drudis.2025.104299
Khalid Rashid , Holger Kalthoff , Sarki A. Abdulkadir , Dieter Adam
{"title":"Death ligand receptor (DLR) signaling: Its non-apoptotic functions in cancer and the consequences of DLR-directed therapies","authors":"Khalid Rashid ,&nbsp;Holger Kalthoff ,&nbsp;Sarki A. Abdulkadir ,&nbsp;Dieter Adam","doi":"10.1016/j.drudis.2025.104299","DOIUrl":"10.1016/j.drudis.2025.104299","url":null,"abstract":"<div><div>Death ligands (DLs), particularly tumor necrosis factor alpha (TNF-α), FAS ligand (FASL), and TNF-related apoptosis-inducing ligand (TRAIL), collectively termed TFT, are pivotal members of the TNF superfamily. While traditionally linked to apoptosis, TFT proteins have emerged as key regulators of various non-apoptotic processes. This review summarizes the non-apoptotic functions of TFT in cancer and explores the intricate crosstalk signaling pathways and their impact on nuclear factor kappa B (NF-κB) signaling, inflammation, and pro-tumorigenic function. It also highlights the potential connections and hurdles that exist in translating synthetic lethality strategies involving DLs into clinical applications. Lastly, it discusses the challenges and opportunities associated with TFT-targeted therapeutic strategies for both malignant and non-malignant diseases.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 2","pages":"Article 104299"},"PeriodicalIF":6.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021440","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 impact of operational trial approaches on representativeness: Comparison of decentralized clinical trial participants, conventional trial participants, and patients in daily practice 操作试验方法对代表性的影响：分散临床试验参与者、常规试验参与者和日常实践患者的比较。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-02-01 DOI: 10.1016/j.drudis.2025.104304
Amos J. de Jong , Mira G.P. Zuidgeest , Yared Santa-Ana-Tellez , Christine E. Hallgreen , Thomas T. van Sloten , Anthonius de Boer , Helga Gardarsdottir , the Trials@Home Consortium
{"title":"The impact of operational trial approaches on representativeness: Comparison of decentralized clinical trial participants, conventional trial participants, and patients in daily practice","authors":"Amos J. de Jong ,&nbsp;Mira G.P. Zuidgeest ,&nbsp;Yared Santa-Ana-Tellez ,&nbsp;Christine E. Hallgreen ,&nbsp;Thomas T. van Sloten ,&nbsp;Anthonius de Boer ,&nbsp;Helga Gardarsdottir ,&nbsp;the Trials@Home Consortium","doi":"10.1016/j.drudis.2025.104304","DOIUrl":"10.1016/j.drudis.2025.104304","url":null,"abstract":"<div><div>Decentralized clinical trial (DCT) approaches – in which trial activities are conducted at participants’ homes – have the potential to improve representativeness. We present a study that compared the demographics and cardiovascular risk factors of participants from a DCT (ASCEND) and a conventional trial with a similar trial objective (POPADAD) to those of patients in daily practice. We adjudicate that there are relevant differences when comparing the participants of the conventional trial and the DCT, with the latter providing better representativeness in terms of age, insulin use, smoking status, and body mass index, whereas conventional trial participants were more representative in terms of biological sex. Differences in these characteristics were not explained by the eligibility criteria, but are considered attributable to the operational trial approach.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 2","pages":"Article 104304"},"PeriodicalIF":6.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062742","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
Applications and emerging challenges of single-cell RNA sequencing technology in tumor drug discovery 单细胞RNA测序技术在肿瘤药物发现中的应用和新挑战。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-02-01 DOI: 10.1016/j.drudis.2025.104290
Lu Zhang , Yueying Yang , Jianjun Tan
{"title":"Applications and emerging challenges of single-cell RNA sequencing technology in tumor drug discovery","authors":"Lu Zhang ,&nbsp;Yueying Yang ,&nbsp;Jianjun Tan","doi":"10.1016/j.drudis.2025.104290","DOIUrl":"10.1016/j.drudis.2025.104290","url":null,"abstract":"<div><div>Current therapeutic drugs are inadequate for curing tumors, highlighting the need for novel tumor drugs. The advancement of single-cell RNA sequencing (scRNA-seq) technology offers new opportunities for tumor drug discovery. This technology allows us to explore tumor heterogeneity and developmental mechanisms at the single-cell level. In this review, we outline the application of scRNA-seq in tumor drug discovery stages, including elucidating tumor mechanisms, identifying targets, screening drugs, and understanding drug action and resistance. We also discuss the challenges and future prospects of using scRNA-seq in drug development, providing a scientific foundation for advancing tumor therapies.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 2","pages":"Article 104290"},"PeriodicalIF":6.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997219","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 case study assessing the impact of M&A and licensing on FDA drug approvals of leading pharmaceutical companies 一项案例研究，评估并购和许可对美国食品及药物管理局批准领先制药公司药品的影响。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-02-01 DOI: 10.1016/j.drudis.2025.104306
Alexander Schuhmacher , Kyrylo Grinchenko , Oliver Gassmann , Dominik Hartl , Markus Hinder
{"title":"A case study assessing the impact of M&A and licensing on FDA drug approvals of leading pharmaceutical companies","authors":"Alexander Schuhmacher ,&nbsp;Kyrylo Grinchenko ,&nbsp;Oliver Gassmann ,&nbsp;Dominik Hartl ,&nbsp;Markus Hinder","doi":"10.1016/j.drudis.2025.104306","DOIUrl":"10.1016/j.drudis.2025.104306","url":null,"abstract":"<div><div>Despite a recent increase in FDA new drug approvals, leading pharmaceutical companies continue to face R&amp;D productivity challenges. This highlights the need to better understand the context of their R&amp;D concepts and related R&amp;D outputs. Consequently, we conducted a systematic assessment of the impact of R&amp;D expenditures, R&amp;D intensities, mergers &amp; acquisitions (M&amp;A) deals and licensing agreements on new drug approvals of leading pharmaceutical companies between 2012 and 2021. Our analysis provides key insights into differentiating R&amp;D factors: whereas R&amp;D expenditures and the number of M&amp;A deals correlate with the number of new drug approvals, our analysis shows no correlation with R&amp;D intensity or the number of licensing agreements.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 3","pages":"Article 104306"},"PeriodicalIF":6.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121672","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
Artificial intelligence in peptide-based drug design 人工智能在肽类药物设计中的应用。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-02-01 DOI: 10.1016/j.drudis.2025.104300
Silong Zhai , Tiantao Liu , Shaolong Lin , Dan Li , Huanxiang Liu , Xiaojun Yao , Tingjun Hou
{"title":"Artificial intelligence in peptide-based drug design","authors":"Silong Zhai ,&nbsp;Tiantao Liu ,&nbsp;Shaolong Lin ,&nbsp;Dan Li ,&nbsp;Huanxiang Liu ,&nbsp;Xiaojun Yao ,&nbsp;Tingjun Hou","doi":"10.1016/j.drudis.2025.104300","DOIUrl":"10.1016/j.drudis.2025.104300","url":null,"abstract":"<div><div>Protein–protein interactions (PPIs) are fundamental to a variety of biological processes, but targeting them with small molecules is challenging because of their large and complex interaction interfaces. However, peptides have emerged as highly promising modulators of PPIs, because they can bind to protein surfaces with high affinity and specificity. Nonetheless, computational peptide design remains difficult, hindered by the intrinsic flexibility of peptides and the substantial computational resources required. Recent advances in artificial intelligence (AI) are paving new paths for peptide-based drug design. In this review, we explore the advanced deep generative models for designing target-specific peptide binders, highlight key challenges, and offer insights into the future direction of this rapidly evolving field.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 2","pages":"Article 104300"},"PeriodicalIF":6.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021436","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
Philanthropic drug development: understanding its importance, mechanisms, and future prospects 慈善药物开发：了解其重要性、机制和未来前景。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2025-02-01 DOI: 10.1016/j.drudis.2025.104298
Marc Reichel , Eva M. Murauer , Martin Steiner , Christoph Coch , Hubert Trübel
{"title":"Philanthropic drug development: understanding its importance, mechanisms, and future prospects","authors":"Marc Reichel ,&nbsp;Eva M. Murauer ,&nbsp;Martin Steiner ,&nbsp;Christoph Coch ,&nbsp;Hubert Trübel","doi":"10.1016/j.drudis.2025.104298","DOIUrl":"10.1016/j.drudis.2025.104298","url":null,"abstract":"<div><div>Philanthropic drug development (PDD) addresses gaps in traditional pharmaceutical innovation, particularly for rare and underserved diseases. Cost and timeline challenges discourage new investments, especially in niche therapeutic areas. Patient organizations (POs) are uniquely positioned to help to reduce development challenges by providing expertise, supporting early research, fostering collaborations, and driving patient-centered clinical trials. PDD relies on effective partnerships between POs, pharmaceutical companies, and other stakeholders, ensuring that patient perspectives inform the drug development process. PDD is poised to relieve the pressure on the traditional drug development process and thereby foster beneficial patient-focused innovations. In doing so, PDD allows pharmaceutical companies to expand their drug development activities into commercially unrewarding {} areas, diversifying their portfolios beyond competitive fields.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 2","pages":"Article 104298"},"PeriodicalIF":6.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027497","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
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