European Journal of Medicinal Chemistry最新文献_第9页

Novel dual-functional peptides designed via NanoBiT spike pseudovirus system for real-time monitoring and inhibition of SARS-CoV-2 infection 利用NanoBiT刺突假病毒系统设计的新型双功能肽，用于实时监测和抑制SARS-CoV-2感染

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry

Pub Date : 2026-01-08 DOI: 10.1016/j.ejmech.2026.118568

Cheng-Han Lin , Hua-Hsin Chiang , Xin-Rui Yang , Tzu-Ching Lin , Chin-Hung Tsai , Chih-Sheng Lin

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiates viral infection by binding its surface spike protein to the human angiotensin-converting enzyme 2 (hACE2) receptor. Precise delineation of spike–hACE2 engagement is essential for viral entry and a prime target for therapeutic intervention. However, the current antiviral strategies provided only endpoint readouts and delayed the prioritization against emerging variants. Here, this study introduced novel antiviral compounds designed via a NanoLuc Binary Technology-based pseudovirus [NanoBiT; a structural complementation reporter composed of a Large BiT (LgBiT) and a Small BiT (SmBiT)]. Upon Omicron BA.2-SmBiT spike pseudoviruses infecting LgBiT–hACE2 cells, reconstituted NanoLuc generated quantifiable bioluminescence for real-time spike–hACE2 interaction during viral infection. Within this framework, dual-functional theranostic Anti-spike peptide (S7; ACTPHVSPTHCS) and the Anti-hACE2 peptide (A6; WSTDPGAHLRDY) were identified that not only inhibit SARS-CoV-2 entry by targeting spike and hACE2 proteins, but also serve as diagnostic probes for real-time monitoring. Under optimized conditions, significant inhibition of virus infection was validated in both Anti-spike peptide-treated pseudovirus and Anti-hACE2 peptide-treated hACE2 cells, with a synergistic score of 17.092. Cross-variant efficacy extended to the Omicron JN.1 lineage using a newly constructed JN.1-SmBiT pseudovirus, with molecular docking supporting binding at conserved residues. LgBiT–hACE2 transgenic mice and noninvasive bioluminescence imaging verified in vivo suppression and demonstrated enhanced inhibition with combined treatment. This programmable peptide–NanoBiT framework provided multifunctional compounds that integrate therapeutic efficacy with diagnostic capability. Importantly, the modular design highlights its adaptability to other virus–receptor interactions to underscore its potential in pandemic preparedness.

严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）通过将其表面刺突蛋白与人血管紧张素转换酶2 （hACE2）受体结合而引发病毒感染。精确描述棘突- hace2接合对于病毒进入和治疗干预的主要目标至关重要。然而，目前的抗病毒策略仅提供终点读数，并且延迟了针对新出现变体的优先级。在这里，本研究介绍了通过基于NanoLuc二进制技术的假病毒设计的新型抗病毒化合物[NanoBiT；由大比特（Large BiT, LgBiT）和小比特（Small BiT, SmBiT）组成的结构互补报告器。当Omicron BA.2-SmBiT刺突假病毒感染lbit - hace2细胞时，重组的NanoLuc产生可量化的生物发光，用于病毒感染期间刺突- hace2的实时相互作用。在此框架下，鉴定出双功能治疗性抗刺突肽（S7； ACTPHVSPTHCS）和抗hACE2肽（A6； WSTDPGAHLRDY）不仅可以通过靶向刺突和hACE2蛋白抑制SARS-CoV-2的进入，还可以作为实时监测的诊断探针。在优化后的条件下，抗刺突肽处理的假病毒和抗hACE2肽处理的hACE2细胞均能显著抑制病毒感染，协同评分为17.092。使用新构建的JN.1- smbit假病毒，交叉变异效应扩展到Omicron JN.1谱系，分子对接支持在保守残基上结合。lbit - hace2转基因小鼠和无创生物发光成像证实了体内抑制作用，并显示出联合治疗的增强抑制作用。这种可编程肽-纳米比特框架提供了多功能化合物，将治疗效果与诊断能力结合起来。重要的是，模块化设计突出了其对其他病毒受体相互作用的适应性，从而强调了其在大流行防范方面的潜力。

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引用次数: 0

Trivalent triterpenoids block SARS-CoV-2 and influenza A virus infection by directly targeting homotrimeric envelope proteins 三价三萜通过直接靶向同源三聚体包膜蛋白阻断SARS-CoV-2和甲型流感病毒感染

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry

Pub Date : 2026-01-08 DOI: 10.1016/j.ejmech.2026.118566

Liwen Hua , Mengyang Wang , Qianqian Gao , Honggao Duan , Yiming Wang , Rui Feng , Yiping Zhong , Xingxing Zhu , Yu Mu , Yongmin Zhang , Demin Zhou , Sulong Xiao

Both SARS-CoV-2 and influenza viruses are major causes of contagious respiratory disease, posing a significant challenge to global public health. In previous work, we identified a class of triterpenoids with broad-spectrum antiviral activity by manipulating virus-host fusion. Here we further report the design and synthesis of 24 trivalent triterpenoid derivatives by targeting the homotrimeric spike protein of SARS-CoV-2 and hemagglutinin (HA) of influenza virus. Anti-SARS-CoV-2 pseudovirus screening in HEK293T-ACE2 cells identified two derivatives 18d and 20c as potent entry inhibitors with IC₅₀ values of 0.82 μM and 0.36 μM, respectively, and negligible cytotoxicity. Flow cytometry and surface plasmon resonance (SPR) assays confirmed that these compounds block viral entry by directly binding to the spike protein. Notably, compound 20c also exhibited potent anti-influenza A virus activity in MDCK cells with EC₅₀ value of 0.61 μM. Time-of-addition and SPR assays revealed that 20c acts at the early stage of infection, significantly suppressing HA expression. Molecular docking simulations further elucidated that the binding mode of triterpenoid moiety within the binding pocket of HA and identified key residues involved in the interaction. Collectively, our findings suggest that trivalent triterpenoid derivatives represent a promising class of broad-spectrum antiviral entry agents that inhibit the entry of both SARS-CoV-2 and influenza virus by targeting the homotrimeric envelope proteins.

SARS-CoV-2和流感病毒都是传染性呼吸道疾病的主要病因，对全球公共卫生构成重大挑战。在以前的工作中，我们通过操纵病毒-宿主融合鉴定了一类具有广谱抗病毒活性的三萜。本文进一步以SARS-CoV-2的同三聚体刺突蛋白和流感病毒的血凝素（HA）为靶点，设计合成了24个三价三萜衍生物。在HEK293T-ACE2细胞中进行抗sars - cov -2假病毒筛选，发现两个衍生物18d和20c是有效的进入抑制剂，EC50值分别为0.82 μM和0.36 μM，细胞毒性可以忽略。流式细胞术和表面等离子体共振（SPR）实验证实，这些化合物通过直接与刺突蛋白结合来阻止病毒进入。值得注意的是，化合物20c在MDCK细胞中也表现出较强的抗甲型流感病毒活性，EC50值为0.61 μM。添加时间和SPR分析显示，20c在感染早期起作用，显著抑制HA表达。分子对接模拟进一步阐明了HA结合袋内三萜片段的结合模式，并确定了参与相互作用的关键残基。总之，我们的研究结果表明，三价三萜衍生物代表了一类有前途的广谱抗病毒进入剂，可以通过靶向同源三聚体包膜蛋白来抑制SARS-CoV-2和流感病毒的进入。

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引用次数: 0

A novel luteinizing hormone-releasing hormone (LHRH) receptor-targeting peptide LHRH-III': Design and application for targeted breast cancer therapy 一种新的促黄体生成素释放激素受体靶向肽LHRH- iii '：用于乳腺癌靶向治疗的设计与应用

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry

Pub Date : 2026-01-07 DOI: 10.1016/j.ejmech.2026.118563

Boxiang Qiu , Ruihua Fan , Guangxu Si , Jing Wang , Kailun Wang , Guojun Zheng , Xinxin Tian

Breast cancer is one of the most common malignant tumors among women, with approximately 50–60 % of cases overexpressing the luteinizing hormone-releasing hormone receptor (LHRH-R), making it an important therapeutic target. To overcome the limitations of conventional chemotherapy, this study designed and synthesized a novel LHRH-R-targeting peptide, LHRH-III′, based on the structure of natural LHRH-III with rational structural modifications. Fluorescence labeling experiments demonstrated that this peptide binds to 4T1 cells with an affinity comparable to or superior to that of the classical LHRH-R targeting peptide [D-Lys⁶]-LHRH-I, while its cellular internalization efficiency was increased by more than 6-fold. Subsequently, LHRH-III′ was conjugated to camptothecin (CPT) or doxorubicin (Dox) via a disulfide bond linker to construct peptide-drug conjugates (PDCs). Among these conjugates, LHRH-III′–SS–CPT exhibited more efficient glutathione (GSH)-responsive drug release than LHRH-III′–SS–Dox. In antitumor evaluations, LHRH-III′–SS–CPT demonstrated significant antitumor activity both in vitro and in vivo. Biodistribution studies revealed that hepatic accumulation of LHRH-III′ was only one-sixth of that observed with the control peptide [D-Lys⁶]-LHRH-I, substantially reducing the risk of potential hepatotoxicity caused by off-target accumulation. In summary, the novel targeting peptide LHRH-III′ developed in this study exhibits excellent targeting capability for breast cancer. The lead PDC based on LHRH-III′ (LHRH-III′–SS–CPT) demonstrate promising antitumor efficacy and low toxicity, highlighting their potential application value as a targeted therapeutic strategy for breast cancer.

乳腺癌是女性最常见的恶性肿瘤之一，约有50 - 60%的病例过表达促黄体激素释放激素受体（LHRH-R），使其成为重要的治疗靶点。为了克服常规化疗的局限性，本研究以天然LHRH-III的结构为基础，经过合理的结构修饰，设计合成了一种新型的lhrh - r靶向肽LHRH-III’。荧光标记实验表明，该肽与4T1细胞结合的亲和力与经典的LHRH-R靶向肽[D-Lys6]-LHRH-I相当或优于后者，其细胞内化效率提高了6倍以上。随后，LHRH-III '通过二硫键连接物与喜树碱（CPT）或阿霉素（Dox）偶联，构建肽-药物偶联物（PDCs）。在这些偶联物中，LHRH-III ' -SS-CPT比LHRH-III ' -SS-Dox表现出更有效的谷胱甘肽（GSH）反应性药物释放。在抗肿瘤评价中，LHRH-III′-SS-CPT在体内和体外均表现出显著的抗肿瘤活性。生物分布研究显示，LHRH-III '的肝脏蓄积仅为对照肽[D-Lys6]-LHRH-I的六分之一，大大降低了脱靶蓄积引起的潜在肝毒性风险。综上所述，本研究开发的新型靶向肽LHRH-III '对乳腺癌具有良好的靶向能力。基于LHRH-III ' （LHRH-III ' -SS-CPT）的先导PDC具有良好的抗肿瘤疗效和低毒性，作为乳腺癌靶向治疗策略具有潜在的应用价值。

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引用次数: 0

Flavonoids as promising drug leads: Structural diversity, synthetic strategies, and drug-likeness optimization 黄酮类化合物作为有前途的药物先导物：结构多样性、合成策略和药物相似性优化

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry

Pub Date : 2026-01-06 DOI: 10.1016/j.ejmech.2025.118549

Chao Yang, Qing Gong, Rong Zhu, Yufan Fan, Qiumeng Wang, Guangbo Ge, Ping Wang

Flavonoids are a major class of natural polyphenolic compounds with diverse physiological and pharmacological activities, and their privileged scaffolds have long attracted interest in natural product based drug discovery. As their physicochemical properties and biological functions are strongly structure-dependent, variations in substitution patterns can markedly influence solubility, membrane permeability, metabolic stability and overall bioactivity. However, the relationships between structural diversity, functional activities, and druggability remain insufficiently summarized. In this review, the biological activities associated with four representative flavonoid subclasses, including flavones, isoflavones, flavonols, and dihydroflavones, are first summarized. It then focuses on the chemical synthesis of these core scaffolds, systematically reviewing the main synthetic strategies developed over the past two decades and comparing their efficiency, safety, and practical feasibility. Given that poor solubility and limited metabolic stability commonly restrict the drug-likeness of natural flavonoids, the review further examines how structural modifications influence physicochemical and pharmacokinetic properties, and summarizes strategies for selective methylation, acylation, glycosylation, halogenation, and arylation. Finally, the structure-activity relationships (SARs) of representative flavonoids are summarized to guide rational structural optimization and the design of improved flavonoid derived drug candidates. Overall, this review integrates advances in pharmacology, synthetic chemistry, and medicinal chemistry, providing strategic insights for the future development of flavonoid based therapeutics.

黄酮类化合物是一类重要的天然多酚类化合物，具有多种生理和药理活性，其优越的支架结构长期以来引起了天然产物药物开发的兴趣。由于它们的理化性质和生物学功能强烈依赖于结构，取代模式的变化可以显著影响溶解度、膜通透性、代谢稳定性和整体生物活性。然而，结构多样性、功能活性和可药物性之间的关系仍然没有得到充分的总结。本文首先综述了黄酮类、异黄酮类、黄酮醇类和二氢黄酮类四种具有代表性的类黄酮亚类的生物活性。然后重点介绍了这些核心支架的化学合成，系统地回顾了过去二十年来发展起来的主要合成策略，并比较了它们的效率、安全性和实际可行性。鉴于水溶性差和有限的代谢稳定性通常限制了天然黄酮类化合物的药物相似性，本文进一步研究了结构修饰如何影响其物理化学和药代动力学性质，并总结了选择性甲基化、酰化、糖基化、卤化和芳基化的策略。最后，总结了代表性黄酮类化合物的构效关系，为合理优化结构和设计改进的类黄酮衍生候选药物提供指导。综上所述，本文综述了类黄酮在药理学、合成化学和药物化学方面的研究进展，为未来类黄酮治疗药物的发展提供了战略见解。

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引用次数: 0

An overview of KRAS G12D inhibitors: Expanding the therapeutic frontier of KRAS in targeting KRAS G12D using diverse therapeutic modalities KRAS G12D抑制剂综述：利用多种治疗方式，扩大KRAS靶向KRAS G12D的治疗前沿

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry

Pub Date : 2026-01-06 DOI: 10.1016/j.ejmech.2025.118555

Varun Kumar, Abhinandan K. Danodia, Pradeep S. Jadhavar, Subhendu K. Mohanty, Swapan K. Samanta

引用次数: 0

α-Ketoamides-based covalent inhibitors in drug discovery: Current status and synthetic methods 基于α-酮酰胺的共价抑制剂的药物发现：现状和合成方法

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry

Pub Date : 2026-01-05 DOI: 10.1016/j.ejmech.2026.118558

Ho Ying Huang, Nicolas Moitessier

The α-ketoamide moiety is abundant in natural products and has been incorporated by medicinal chemists into novel potential drug candidates. A variety of synthetic methods for preparing this privileged functional group have been disclosed. In this review, we will provide insights into the chemical reactivity of α-ketoamides, their successful incorporation into potent covalent inhibitors and an overview of the synthetic methodologies that are actively used in the discovery of small molecule α-ketoamide covalent inhibitors. Finally, this perspective aims to help medicinal chemists in overcoming synthetic challenges when introducing α-ketoamide groups into more efficient hit/lead molecules, and to highlight the popularity of α-ketoamide in drug design and development.

α-酮酰胺部分在天然产物中含量丰富，已被药物化学家纳入新的潜在候选药物中。已经公开了用于制备该特权官能团的多种合成方法。在这篇综述中，我们将提供对α-酮酰胺的化学反应性的见解，它们成功地结合到有效的共价抑制剂中，并概述了积极用于发现小分子α-酮酰胺共价抑制剂的合成方法。最后，这一视角旨在帮助药物化学家在将α-酮酰胺基团引入更有效的hit/lead分子时克服合成挑战，并突出α-酮酰胺在药物设计和开发中的受欢迎程度。

引用次数: 0

Small-molecule drug discovery targeting the orphan G protein-coupled receptor GPR84 as potential therapeutics 靶向孤儿G蛋白偶联受体GPR84的小分子药物的发现作为潜在的治疗方法

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry

Pub Date : 2026-01-05 DOI: 10.1016/j.ejmech.2026.118561

Binghan Xue , Yao Xiao , Weipeng Hu , Fangli Zhou , Bowen Zhang , Yiwen Zhang

GPR84 (EX33), a member of the rhodopsin family of G protein-coupled receptors, has been implicated in inflammatory and fibrotic diseases through its roles in immune cell function, making it a promising therapeutic target. Consequently, targeting GPR84 represents a potential strategy for treating a range of related diseases. Despite the advancement of several GPR84-targeting small molecules like DIM into clinical trials, none have gained market approval. Therefore, exploring novel chemical scaffolds is essential for drug discovery targeting GPR84. However, the structure and mechanism of GPR84 remain poorly understood, impeding the development of small-molecule therapeutics targeting GPR84. This perspective delves into the structure, function, and mechanisms of GPR84, examines its disease associations and therapeutic prospects, and surveys the current clinical landscape. It highlights the analysis of structure-activity relationships and the hallmarks of known GPR84 scaffolds, providing a proposed set of molecular design principles, for developing next-generation agonists and antagonists with superior efficacy and selectivity.

GPR84 （EX33）是G蛋白偶联受体视紫红质家族的成员，通过其在免疫细胞功能中的作用与炎症和纤维化疾病有关，使其成为一个有希望的治疗靶点。因此，靶向GPR84代表了治疗一系列相关疾病的潜在策略。尽管一些靶向gpr84的小分子药物如DIM已进入临床试验阶段，但尚未获得市场批准。因此，寻找新的化学支架对于发现靶向GPR84的药物至关重要。然而，目前对GPR84的结构和机制知之甚少，这阻碍了靶向GPR84的小分子治疗药物的发展。本文将深入探讨GPR84的结构、功能和机制，探讨其疾病关联和治疗前景，并调查当前的临床前景。本文重点分析了已知GPR84支架的结构-活性关系和特点，为开发具有优越疗效和选择性的下一代激动剂和拮抗剂提供了一套分子设计原则。

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引用次数: 0

2-Naphthyl tetrazoles are potent antiproliferative and apoptotic inducers with different tubulin polymerization dynamics inhibitory activity 2-萘基四唑是有效的抗增殖和凋亡诱导剂，具有不同的微管蛋白聚合动力学抑制活性。

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry

Pub Date : 2026-01-05 DOI: 10.1016/j.ejmech.2025.118554

Miguel Marín , Laura Gallego-Yerga , Dominik Fachet , Raúl Fuentes-Martín , Silvia González-Pelayo , Simone Reber , Rafael Peláez

Microtubule-targeting agents continue to be a cornerstone of cancer treatment; however, issues like systemic toxicity, poor metabolic stability, and multidrug resistance often restrict their effectiveness. Identifying new molecules that can overcome these limitations is crucial for enhancing therapeutic outcomes. In this work, we present a library of 12 new tubulin-binding compounds, analogues of Combretastatin A-4, incorporating a tetrazole bridge designed to preserve the cisoid disposition required for binding to the colchicine site. These compounds were assayed against a wide range of cancer cell lines, with compounds 23, 31, and 32 showing antiproliferative potencies in the low nanomolar range. The mechanism of action was assessed through microscopy experiments, which confirmed disruption of microtubule polymerization in cells. In vitro microtubule polymerization reactions with tubulin isolated from HEK-293 cells showed that compounds with drastically different inhibitory effects on polymerization dynamics elicit similar antiproliferative effects, thus questioning the usual assumption that interference with microtubule dynamics is the fundamental mechanism behind tubulin inhibitors’ actions. Cell cycle and cell death assays revealed atypical behavior for antimitotic agents, showing less mitotic arrest than typically but a significant increase in apoptotic cell populations, thus suggesting that they trigger cell death in an unusual way. In silico conformational and docking studies supported binding at the colchicine site and suggested favourable pharmacokinetic profiles. Together, these results position these compounds as highly promising candidates for development as new antitumor agents, especially 23 for glioblastoma.

微管靶向药物仍然是癌症治疗的基石；然而，诸如全身毒性、代谢稳定性差和多药耐药等问题往往限制了它们的有效性。发现能够克服这些限制的新分子对于提高治疗效果至关重要。在这项工作中，我们提出了一个包含12个新的微管蛋白结合化合物的文库，这些化合物是Combretastatin a -4的类似物，包含一个四唑桥，旨在保留与秋水仙碱位点结合所需的顺isoid配置。这些化合物对多种癌细胞系进行了检测，化合物23、31和32在低纳摩尔范围内显示出抗增殖能力。通过显微实验评估了作用机制，证实了微管聚合在细胞中的破坏。从HEK-293细胞中分离的微管蛋白在体外进行的微管聚合反应表明，对聚合动力学具有截然不同抑制作用的化合物会产生相似的抗增殖作用，从而质疑了通常认为干扰微管动力学是微管蛋白抑制剂作用背后的基本机制的假设。细胞周期和细胞死亡试验揭示了抗有丝分裂药物的非典型行为，表现出比通常情况下更少的有丝分裂阻滞，但凋亡细胞群显著增加，因此表明它们以一种不寻常的方式触发细胞死亡。硅构象和对接研究支持秋水仙碱位点的结合，并提出了有利的药代动力学特征。总之，这些结果使这些化合物成为开发新的抗肿瘤药物，特别是胶质母细胞瘤的极有希望的候选者。

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引用次数: 0

Recent development of ATR inhibitors for cancer therapy ATR抑制剂在癌症治疗中的最新进展

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry

Pub Date : 2026-01-04 DOI: 10.1016/j.ejmech.2026.118560

Jiao Wang , Yuan Quan , Ying Shen , Liang Chang , Huijie Zhang , Wancheng Zhao

Ataxia Telangiectasia and Rad3-related (ATR) kinase belongs to the PIKK (phosphatidylinositol 3-kinase–related kinase) family and serves as a pivotal hub for preserving genomic stability and regulating responses to replication stress and DNA damage. Dysregulation of ATR signaling is strongly associated with tumorigenesis, resistance to therapy, and other pathological states (such as neurodegenerative diseases), making it a highly attractive target in cancer therapy. To date, no ATR inhibitors have achieved regulatory approval; however, several candidate molecules, most notably berzosertib, ceralasertib, and gartisertib, are advancing in clinical trials. This review focuses on the medicinal chemistry progress in ATR inhibitor development since 2018. Throughout this review, we systematically interweave major chemical scaffolds. We anticipate that this review will offer insightful guidance for rational design of future ATR inhibitors and help accelerate the emergence of next-generation ATR inhibitors with superior potency, selectivity, and clinical feasibility.

共济失调毛细血管扩张和rad3相关激酶（ATR）属于PIKK（磷脂酰肌醇3激酶相关激酶）家族，是保持基因组稳定性和调节复制应激和DNA损伤反应的关键枢纽。ATR信号的失调与肿瘤发生、治疗抵抗和其他病理状态（如神经退行性疾病）密切相关，使其成为癌症治疗中极具吸引力的靶点。到目前为止，还没有ATR抑制剂获得监管部门的批准；然而，一些候选分子，最著名的是berzosertib， ceralasertib和gartisertib，正在进行临床试验。本文综述了2018年以来ATR抑制剂的药物化学研究进展。在这篇综述中，我们系统地交织了主要的化学支架。我们期望这篇综述将为未来ATR抑制剂的合理设计提供有洞察力的指导，并有助于加速出现具有优越效力、选择性和临床可行性的下一代ATR抑制剂。

引用次数: 0

Recent progress of napabucasin as privileged scaffold in the discovery of anticancer agents 油菜素作为特殊支架在抗癌药物发现中的最新进展

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry

Pub Date : 2026-01-04 DOI: 10.1016/j.ejmech.2026.118559

Xiaojuan Yang , Guoyang Ma

Cancer is a major health issue worldwide, necessitating the development of novel treatments because treating this disease is challenging. Napabucasin, a furan-fused 1,4-naphthoquinone, exhibits significant anticancer activity through various molecular mechanisms and has become a privileged scaffold for developing antitumor therapeutics. In this review, we systematically evaluated recent progress in the use of napabucasin as a privileged scaffold for the discovery of antitumor drugs, focusing on structure-activity relationships (SARs), structural modification strategies, and the illustration of tumor inhibitory pathways from a mechanistic perspective. By conducting multidimensional assessments, we propose feasible directions for developing napabucasins with improved pharmacological properties for cancer treatment.

癌症是世界范围内的一个主要健康问题，需要开发新的治疗方法，因为治疗这种疾病具有挑战性。Napabucasin是一种呋喃融合的1,4-萘醌，通过多种分子机制显示出显著的抗癌活性，已成为开发抗肿瘤治疗药物的优越支架。在这篇综述中，我们系统地评估了近年来将napabucasin作为发现抗肿瘤药物的特殊支架的进展，重点是结构-活性关系（SARs），结构修饰策略，以及从机制角度说明肿瘤抑制途径。通过多维度评估，我们提出了开发具有改进药理特性的纳布卡霉素用于癌症治疗的可行方向。

引用次数: 0