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Carbon dots in oncology: multifunctional nanoplatforms for diagnosis, targeted therapy, and drug discovery 肿瘤中的碳点：用于诊断、靶向治疗和药物发现的多功能纳米平台。
IF 7.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Drug Discovery Today
Pub Date : 2025-10-01 DOI: 10.1016/j.drudis.2025.104470
Sandra Rodríguez-Varillas , Jorge Espina-Casado , Rosana Badía Laíño , Alfonso Fernández-González , Tania Fontanil López
Carbon dots (CDs) are emerging nanomaterials with unique optical and biological properties that position them as highly promising candidates in precision oncology. Their small size, biocompatibility, fluorescence, and capacity for surface functionalization enable diverse applications, including tumor imaging, targeted drug delivery, gene therapy, and photothermal or photodynamic therapy (PTT/PDT). CDs have demonstrated efficacy in fluorescence and magnetic resonance imaging (MRI), facilitating early tumor detection. As drug carriers and gene delivery systems, they offer controlled and targeted release with reduced toxicity. In addition, CDs support early-phase drug discovery by improving solubility and bioavailability, and enabling real-time tracking. Despite these promising results, their clinical translation remains limited by variability in synthesis methods and an incomplete understanding of their structure–function relationships.
碳点（cd）是一种新兴的纳米材料，具有独特的光学和生物学特性，在精确肿瘤学中具有很高的应用前景。它们的小尺寸、生物相容性、荧光性和表面功能化能力使其具有多种应用，包括肿瘤成像、靶向药物递送、基因治疗、光热或光动力治疗（PTT/PDT）。cd在荧光和磁共振成像（MRI）中显示出有效性，有助于早期肿瘤检测。作为药物载体和基因传递系统，它们提供了降低毒性的可控和靶向释放。此外，CDs通过改善溶解度和生物利用度以及实现实时跟踪来支持早期药物发现。尽管有这些有希望的结果，但它们的临床翻译仍然受到合成方法的可变性和对其结构-功能关系的不完全理解的限制。
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引用次数: 0
Harnessing zebrafish as a model for photopharmacology: Insights into light-controlled biological effects of photoswitchable drugs 利用斑马鱼作为光药理学的模型：对光转换药物的光控生物效应的见解。
IF 7.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Drug Discovery Today
Pub Date : 2025-10-01 DOI: 10.1016/j.drudis.2025.104477
Guilherme Pietro da Silva , Janine Doorduin , Wiktor Szymanski , Rosane Souza da Silva , Philip Elsinga , Carla Denise Bonan
Photopharmacology is an emerging field of pharmacological sciences that enables precise spatiotemporal control over drug activation with light. In its reversible mode, it relies on photoswitchable bioactive compounds. The capacity to reversibly activate and deactivate drugs derivatized with photoswitches enables us to avoid side effects and environmental toxicity. Zebrafish represent an emerging and privileged model for translational photopharmacology because of their optical transparency at early developmental stages, genetic tractability, and well-characterized biological mechanisms. In this review, we discuss the use of zebrafish in advancing photopharmacology and understanding the effects of light-controlled interventions using photoswitchable bioactive compounds.
光药理学是一个新兴的药理学领域，它能够对药物的光激活进行精确的时空控制。在可逆模式下，它依赖于光切换的生物活性化合物。可逆激活和灭活由光开关衍生的药物的能力使我们能够避免副作用和环境毒性。斑马鱼由于其在早期发育阶段的光学透明性、遗传易感性和良好的生物学机制特征，代表了一种新兴的、优越的翻译光药理学模型。在这篇综述中，我们讨论了斑马鱼在推进光药理学和理解利用光切换生物活性化合物进行光控干预的作用方面的应用。
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引用次数: 0
Corrigendum to “Targeting mutant EGFR in non-small cell lung cancer in the context of cell adaptation and resistance” [Drug Discov. Today 30(7) (2025) 104407] “在细胞适应和耐药的背景下靶向非小细胞肺癌中的突变EGFR”[药物发现]的勘误表。今天30(7)(2025)104407]。
IF 7.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Drug Discovery Today
Pub Date : 2025-10-01 DOI: 10.1016/j.drudis.2025.104426
Selene K. Roberts , Ioannis Galgadas , David T. Clarke , Laura C. Zanetti-Domingues , Francesco L. Gervasio , Marisa L. Martin-Fernandez
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引用次数: 0
RNA virus and DNA virus initiations of autoimmune diseases and/or dementias 自身免疫性疾病和/或痴呆的RNA病毒和DNA病毒启动。
IF 7.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Drug Discovery Today
Pub Date : 2025-09-24 DOI: 10.1016/j.drudis.2025.104481
Kevin Roe
There are viral pathogen pathways to initiate autoimmune diseases, such as multiple sclerosis, directly or indirectly, by reactivating latent viruses including human herpesviruses. After initial infections, these DNA viruses can enter latency but periodically reactivate into active infections following triggers: medical treatments inducing immunosuppressions; and infections by immunosuppressive pathogens including RNA viruses, stress or malnutrition. An indirect causation pathway for autoimmune diseases can utilize immune suppressions by RNA virus infections, which trigger reactivation of latent herpesviruses capable of directly causing autoimmune diseases. Although it is believed that general inflammation, not specific pathogens, causes autoimmune diseases, experimental evidence indicates autoimmune diseases are caused by herpesvirus reactivations. Such viral reactivations can be induced by immunosuppressions during severe pathogen infections, particularly by RNA virus infections.
有一些病毒病原体途径可以直接或间接地通过激活潜伏病毒（包括人类疱疹病毒）引发自身免疫性疾病，如多发性硬化症。在初始感染后，这些DNA病毒可以进入潜伏期，但周期性地重新激活为活动性感染，以下触发因素：药物治疗诱导免疫抑制；免疫抑制病原体感染，包括RNA病毒、压力或营养不良。自身免疫性疾病的间接病因途径可以利用RNA病毒感染的免疫抑制，从而触发能够直接引起自身免疫性疾病的潜伏疱疹病毒的再激活。虽然人们认为是一般的炎症而不是特定的病原体引起自身免疫性疾病，但实验证据表明，自身免疫性疾病是由疱疹病毒再激活引起的。在严重病原体感染期间，特别是RNA病毒感染期间，免疫抑制可诱导这种病毒再激活。
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引用次数: 0
Challenges of broad-spectrum antiviral drug discovery and development for emerging pathogens 新出现病原体的广谱抗病毒药物发现和开发的挑战。
IF 7.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Drug Discovery Today
Pub Date : 2025-09-24 DOI: 10.1016/j.drudis.2025.104486
Holli-Joi Martin , Jon-Michael Beasley , Enes Kelestemur , Zoe Sessions , Stephan Ludwig , Nathaniel J. Moorman , Ralph Baric , Eugene N. Muratov , Alexander Tropsha
Broad-spectrum antiviral agent (BSAA) drugs are essential in the fight against viral, especially emerging, diseases. However, their development faces several challenges including insufficiently focused funding, fragmented research efforts and limited systematic data on BSAAs. In this review, we highlight these challenges, summarize accessible collections of data on antiviral compounds and viral targets, and explore possible directions toward the development of BSAAs. Whereas most existing BSAAs have been discovered serendipitously, we posit that rational, and feasible, design of direct-acting BSAAs should be focused on homologous targets found in viruses within a single viral family.
广谱抗病毒药物（BSAA）在对抗病毒性疾病，特别是新出现的疾病中是必不可少的。然而，它们的发展面临着一些挑战，包括资金不够集中、研究工作分散以及关于BSAAs的系统数据有限。在这篇综述中，我们强调了这些挑战，总结了抗病毒化合物和病毒靶点的可用数据，并探讨了BSAAs的可能发展方向。鉴于大多数现有的BSAAs都是偶然发现的，我们认为合理可行的直接作用BSAAs设计应该集中在单个病毒家族中发现的同源靶标上。
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引用次数: 0
Molecular glues as GPCR modulators: unveiling three distinct mechanistic pathways for signal regulation 分子胶作为GPCR调节剂：揭示信号调节的三种不同的机制途径。
IF 7.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Drug Discovery Today
Pub Date : 2025-09-24 DOI: 10.1016/j.drudis.2025.104484
Yuxuan Xing , Jianyang Ao , Xiaoli Zhu , Zhengjun Chai , Shaoyong Lu
G protein-coupled receptors (GPCRs) constitute a large and pharmaceutically significant family of membrane proteins that mediate a wide range of physiological responses. Conventional modulation strategies primarily target orthosteric sites, but recent studies have identified a novel class of modulators known as ‘molecular glues’ that stabilize specific receptor–transducer interfaces. This review categorizes molecular glues into three mechanistic groups on the basis of their mode of action: those that directly stabilize receptor–transducer complexes, those that induce biased signaling through allosteric interactions, and those that modulate signaling indirectly by targeting allosteric regulatory sites. With advances in structural biology and computational methodologies, molecular glues are increasingly recognized as promising biased agonists, next-generation therapeutic agents, and valuable chemical tools for elucidating GPCR signaling pathways.
G蛋白偶联受体（gpcr）是一个巨大的具有重要医学意义的膜蛋白家族，介导广泛的生理反应。传统的调制策略主要针对正构位，但最近的研究发现了一类被称为“分子胶”的新型调节剂，可以稳定特定的受体-换能器界面。本文根据分子胶的作用方式将其分为三类：直接稳定受体-换能器复合物的分子胶，通过变构相互作用诱导偏倚信号传导的分子胶，以及通过靶向变构调节位点间接调节信号传导的分子胶。随着结构生物学和计算方法的进步，分子胶越来越被认为是有前途的偏向性激动剂，下一代治疗剂，以及阐明GPCR信号通路的有价值的化学工具。
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引用次数: 0
DILIrank 2.0: An updated and expanded database for drug-induced liver injury risk based on FDA labeling and a literature review DILIrank 2.0：一个更新和扩展的基于FDA标签和文献综述的药物性肝损伤风险数据库。
IF 7.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Drug Discovery Today
Pub Date : 2025-09-24 DOI: 10.1016/j.drudis.2025.104485
AyoOluwa O. Olubamiwa , Yanyan Qu , Skylar Connor, Weida Tong, Dongying Li, Minjun Chen
Drug-induced liver injury (DILI) is of great concern in drug development and public health. DILIrank 1.0, a widely used public dataset that ranks FDA-approved drugs by their potential to cause DILI, has significantly enabled the development of new methods for improved DILI assessment. Here, we introduce DILIrank 2.0, an essential update of DILIrank 1.0, to capture new non-biologics drug and liver-related adverse event data generated since its inception 15 years ago. Using DILIrank 2.0, we also observe changes in the DILI profiles of approved drugs following the introduction of different FDA regulatory programs. DILIrank 2.0 is an up-to-date resource that offers opportunities for supporting DILI safety assessment, predictive model development, and evaluation of new approach methods (NAMs).
药物性肝损伤（DILI）在药物开发和公共卫生领域受到广泛关注。DILIrank 1.0是一个广泛使用的公共数据集，根据引起DILI的可能性对fda批准的药物进行排名，极大地促进了改善DILI评估的新方法的开发。在此，我们介绍DILIrank2.0, dilirank1.0的重要更新，以捕获自15年前创建以来产生的新的非生物药物和肝脏相关不良事件数据。使用DILIrank 2.0，我们还观察到在引入不同的FDA监管程序后，已批准药物的DILI概况的变化。DILIrank 2.0是一个最新的资源，为支持DILI安全评估、预测模型开发和新方法（NAMs）的评估提供了机会。
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引用次数: 0
RXFP1, the relaxin receptor: Lost and found in translation 松弛素受体RXFP1：在翻译中丢失和发现。
IF 7.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Drug Discovery Today
Pub Date : 2025-09-23 DOI: 10.1016/j.drudis.2025.104483
Mark Lal , Sean Eddy , Anna Walentinsson , Jeffrey B. Hodgin , Pernille B.L. Hansen , Magnus Althage , Matthias Kretzler
Relaxin, historically recognized as a pregnancy hormone, is today characterized as a circulating protein possessing several cardiovascular modulating and anti-fibrotic properties of high clinical interest. Although it has long been recognized that there exists remarkable species diversity regarding the tissue sources and physiological effects of relaxin, there is a considerable gap in our translational understanding of its signal transducing receptor, relaxin family peptide receptor 1 (RXFP1). Here, we review the topic and highlight the striking contrast in RXFP1 tissue expression from rodents to humans, and describe how a renewed focus on RXFP1 target pharmacology is critical to delivering future clinical success in relation to this physiologically important signaling receptor.
松弛素，历史上被认为是一种妊娠激素，今天被认为是一种循环蛋白，具有多种心血管调节和抗纤维化特性，具有很高的临床价值。虽然人们早就认识到松弛素的组织来源和生理作用存在显著的物种多样性，但我们对其信号转导受体松弛素家族肽受体1 （RXFP1）的翻译理解还存在相当大的差距。在这里，我们回顾了这一主题，并强调了RXFP1组织在啮齿动物和人类之间表达的显著差异，并描述了如何重新关注RXFP1靶点药理学对于提供与这种生理上重要的信号受体相关的未来临床成功至关重要。
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引用次数: 0
Methionine biosynthesis as a key metabolic pathway for antimicrobial drug discovery in Streptococcus mutans 甲硫氨酸的生物合成是变形链球菌发现抗微生物药物的关键代谢途径。
IF 7.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Drug Discovery Today
Pub Date : 2025-09-23 DOI: 10.1016/j.drudis.2025.104482
Kulsum Fatima , Syed A. Ali , Asad U. Khan
Streptococcus mutans, a Gram-positive, facultative anaerobic bacterium, is a key contributor to dental caries. It forms biofilms to colonize the tooth surface, has stress resistance mechanisms to survive the fluctuating oral environment, and produces virulence factors, all of which cause enamel demineralization, acid production, and caries development. Traditional antimicrobial strategies target central metabolic pathways in S. mutans, but most enzymes are conserved between humans and bacteria. However, one prospective approach is to target methionine biosynthesis. This pathway is essential for protein synthesis, methylation reactions, and oxidative stress resistance, supporting bacterial growth, biofilm formation, and cariogenic potential. Notably, its selective inhibition can be achieved because this pathway is absent in humans. Therefore, targeting enzymes of this pathway could halt bacterial growth and virulence, offering a novel antimicrobial strategy to treat S. mutans infections.
变形链球菌是一种革兰氏阳性兼性厌氧细菌，是导致龋齿的主要原因。它在牙齿表面形成生物膜，在波动的口腔环境中生存，并产生毒力因子，所有这些都导致牙釉质脱矿，产酸和龋齿的发展。传统的抗菌策略针对变形链球菌的中心代谢途径，但大多数酶在人与细菌之间是保守的。然而，一种有前景的方法是靶向蛋氨酸生物合成。该途径对蛋白质合成、甲基化反应和氧化应激抵抗、支持细菌生长、生物膜形成和龋齿潜能至关重要。值得注意的是，它的选择性抑制可以实现，因为这种途径在人类中是不存在的。因此，靶向这一途径的酶可以阻止细菌的生长和毒力，为治疗变形链球菌感染提供了一种新的抗菌策略。
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引用次数: 0
Rational discovery of molecular glue degraders based on block chemistry 基于块化学的分子胶水降解剂的合理发现。
IF 7.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Drug Discovery Today
Pub Date : 2025-09-20 DOI: 10.1016/j.drudis.2025.104480
Junjie Wei , Wenjing Feng , Qingsong Chen , Qianbin Li , Zhuo Chen
Molecular glue degraders (MGDs) have emerged as promising therapeutic agents with substantial clinical potential and growing commercial interest in terms of their pharmaceutical development. Nevertheless, the translation of MGDs into clinical trials remains limited. Recent advances in drug discovery technologies are facilitating a paradigm shift in MGD development, from serendipitous discovery to rational design. Here, we systematically analyze rational MGD discovery strategies, focusing on E3 ligase and target ligand modifications. Furthermore, we highlight cutting-edge technologies and the latest trends in MGD development. Thus, this review provide valuable insights for researchers and could help accelerate the clinical translation of MGDs.
分子胶降解剂（MGDs）作为一种有前景的治疗药物，在其药物开发方面具有巨大的临床潜力和日益增长的商业兴趣。然而，将MGDs转化为临床试验仍然有限。药物发现技术的最新进展正在促进MGD发展的范式转变，从偶然发现到理性设计。在此，我们系统地分析了合理的MGD发现策略，重点是E3连接酶和靶配体修饰。此外，我们还重点介绍了MGD发展的前沿技术和最新趋势。因此，本综述为研究人员提供了有价值的见解，并有助于加速MGDs的临床转化。
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引用次数: 0
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