EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY欧洲药物化学杂志
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY(英文缩写 EUR J MED CHEM),ISSN 0223-5234,eISSN 1768-3254,中文译名:欧洲药物化学杂志 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 7.088 | Q1 |
| 2022 | 6.700 | Q1 |
| 2023 | 6.000 | Q1 |
| 2024 | 5.900 | Q1 |
| 2025 | 6.700 | Q1 |
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 最新收录文献
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3. The thiocarbonyl analog of chrysin induces apoptosis and oxidative stress-mediated unfolded protein response in breast cancer cells.
PMID:日期:2026-11-15Natural flavones such as chrysin and baicalein were characterized by a wide range of biological activities including, among others, antioxidant and anticancer action. Nevertheless, their use in biomedical applications is restricted due to limited bioavailability. In the present study, C4 thionation-based approach was considered to produce thiochrysin and thiobaicalein with improved anticancer activity. The thiocarbonyl analogs were tested against breast cancer cells with different receptor status (MCF-7 ER-positive, MDA-MB-231 TNBC, and SK-BR-3 HER2-positive) along with the corresponding normal cells MCF-10F. Thiochrysin, when used at the concentration of 1 μM, sensitized MCF-7 and SK-BR-3 cells to apoptotic cell death compared to the action of parent flavone chrysin that was associated with elevated production of superoxide. Thiochrysin-mediated oxidative stress in MCF-7 cells resulted in the activation of unfolded protein response (UPR) as judged by increased phosphorylated status of IRE1, elevated levels of ATF6 and ER-associated chaperone GRP78. Cytotoxic potential of thiochrysin was also documented using 3D breast cancer cell-based spheroid models. Thiochrysin was also active against doxorubicin-induced senescent and drug-resistant MCF-7 and SK-BR-3 cells. In contrast, anti-breast cancer action of thiobaicalein was less pronounced. In silico approaches such as molecular simulations and ADMET profiling were also used to predict thiochrysin action in in vivo situations. In conclusion, we postulate that C4 thionation may potentiate the anticancer action of selected flavones, here chrysin, based on oxidative stress-mediated apoptosis.
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4. In vivo imaging of lipid nanoparticle messenger RNA therapeutics: Current advances and emerging opportunities.
PMID:日期:2026-11-15Messenger RNA (mRNA) therapeutics formulated in lipid nanoparticles (LNPs) have transformed vaccinology and enabled a versatile platform for protein-based therapy across a wide range of diseases. Despite their clinical success, LNP-encapsulated mRNA (LNP-mRNA) systems are still largely designed through empirical screening due to an incomplete understanding of their in vivo behavior. This review systematically examines how in vivo imaging modalities have been used in the recent literature to interrogate LNP biodistribution, cellular uptake, and functional mRNA expression. Across the studies reviewed, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers have demonstrated that LNP biodistribution, including organ tropism and size-dependent transport, is governed by formulation parameters and route of administration. Liver and spleen accumulation dominate current systemic delivery profiles. Particles in the 20-100 nm range generally favor efficient extravasation, cellular uptake, and lymphatic transport, while larger ones are gradually associated with reduced cellular internalization and increased reliance on cell-mediated transport to reach draining lymph nodes. Quantitative fluorescence and reporter-gene studies identified endosomal escape as the principal intracellular bottleneck, with less than 2% of internalized RNA typically reaching the cytosol. MRI results, although currently limited, have provided coherent evidence while offering a non-invasive approach for longitudinal monitoring of intracellular RNA trafficking. Imaging has also revealed a recurrent disconnect between LNP exposure and protein expression, demonstrating that LNP organ accumulation alone is an inadequate measure of productive delivery. Bioluminescent imaging approaches have enabled tracking of protein expression kinetics, showing that peak expression often occurs within hours post-administration, but varies significantly with ionizable lipid nature. Collectively, the recent literature indicates that in vivo imaging can help connect biodistribution and functional delivery with LNP designs. This review highlights that integrating quantitative in vivo imaging into the LNP-mRNA development pipeline enables mechanistic identification of delivery barriers and supports rational optimization of formulations.
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5. Design, synthesis, and biological evaluation of novel brain-penetrant PARP7 inhibitors for the treatment of ischemic stroke.
PMID:日期:2026-11-15Stroke remains a leading cause of mortality and neurological disability, highlighting the need for new therapeutic strategies. Recent studies have indicated that PARP7 is a novel target for stroke treatment. Herein, we report a series of small-molecule PARP7 inhibitors. Among these compounds, B-6 exhibited potent inhibitory activity on PARP7 (IC = 22.8 nM) and efficient blood-brain barrier (BBB) penetration (B/P = 63.7%). In vivo,B-6 demonstrated efficacy across multiple stroke models, significantly reducing cerebral infarct volume in the rat tMCAO model, and in both the rat tMCAO and mouse dMCAO models, suppressing acute inflammatory cytokine production and promoting sustained neurological and sensorimotor recovery over 21 days. Notably, B-6 retained neuroprotective efficacy when treatment was delayed for up to 12 h after ischemic onset. Cellular studies demonstrated that B-6-mediated PARP7 inhibition was accompanied by reduced neuroinflammation and astrocyte activation, attenuated autophagy-related alterations, and preserved synaptic marker expression. In summary, we have identified a brain-penetrable PARP7 inhibitor, B-6, and utilized it as a tool to further demonstrate that PARP7 could be a potential therapeutic target for stroke.
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6. 3-amino-1,2,4-triazine scaffolds as next-generation PDK inhibitors: Design, mechanistic insights, and efficacy in pancreatic ductal adenocarcinoma.
PMID:日期:2026-11-15Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer characterized by late diagnosis, aggressiveness, metabolic plasticity, and resistance to therapy, underscoring the need for new molecular targets. Pyruvate dehydrogenase kinases (PDKs), particularly PDK1 and PDK4, drive metabolic reprogramming and tumor progression, making them attractive therapeutic targets. However, current PDK inhibitors show limited potency and selectivity. Recent 3-amino-1,2,4-triazine derivatives have demonstrated promising PDK1/PDK4 inhibition and antiproliferative activity in PDAC cells, leading to the design of a new library of sixty triazine compounds, here in reported. Several compounds exhibited strong inhibitory activity against PDK1 and PDK4, with IC values ranging from 0.06 to 1.1 μM, demonstrating markedly higher potency compared to DCA and pronounced isoform selectivity. Molecular modeling and supervised molecular dynamics simulations supported these findings, revealing stable binding of representative compounds within the nucleotide-binding pocket of PDK1, involving key interactions with Asp318, Arg286, and Lys327. Functionally, the compounds displayed potent antiproliferative activity in both KRAS wild-type and mutant PDAC cell lines, with micromolar IC values. In three-dimensional pancreatic cancer spheroid models, the most active derivatives outperformed gemcitabine by approximately threefold and exceeded the activity of DCA-derived PDK inhibitors by ∼1.7-fold. Mechanistically, the novel amino-triazines disrupted the PDK/PDH axis, inducing a metabolic shift toward oxidative phosphorylation, impairing mitochondrial function, and triggering apoptotic cell death in KRAS-mutant PSN-1 cells. Overall, these results identify amino-triazine-based scaffolds as a promising new class of potent and selective PDK inhibitors with significant anticancer potential in pancreatic cancer.
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7. Discovery of IMHDPA derivatives with selective cytotoxicity and autophagy-modulating properties: Structure-activity relationships and mechanistic insights.
7. 发现具有选择性细胞毒性和自噬调节特性的IMHDPA衍生物：结构-活性关系和机制见解PMID:日期:2026-11-15Phenotypic drug discovery enables the identification of compounds with novel mechanisms of action and context-dependent biological activities that may not emerge from target-based approaches. Through high-content phenotypic screening, we identified the (E)-6-(2-((1H-indol-3-yl)methylene)hydrazineyl)-N,N-diethylpyrimidin-4-amine (IMHDPA) scaffold as a potent and highly selective inhibitor of HeLa cell proliferation. To further explore this scaffold, a library of 70 analogues was synthesized, and structure-activity relationship studies revealed stringent structural requirements for maintaining cellular potency and selectivity. Among them, compound 39 emerged as the most active derivative, exhibiting a GI value of 2.96 nM against HeLa cells and an exceptional selectivity index exceeding 16,000-fold across a panel of 15 cell lines. Compound 39 suppressed colony formation, migration, invasion, and spheroid growth, while inducing pronounced morphological alterations in HeLa cells. Mechanistic investigations indicated that its antiproliferative activity was associated with autophagy activation rather than apoptosis, necrosis, ferroptosis, or reactive oxygen species accumulation. Integrated transcriptomic and proteomic analyses implicated perturbation of cholesterol metabolism and inhibition of mTORC1 signaling as potential upstream events linked to autophagy induction. Collectively, these findings establish IMHDPA derivatives as promising chemical probes for investigating the molecular basis of context-dependent autophagy-associated cytotoxicity and support future efforts aimed at elucidating the molecular determinants underlying this selective phenotype.
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8. Discovery of a novel 1H-pyrazole-3-amine derivative 6h with potent antitumor activity by targeting tubulin and FLT3.
8. 通过靶向微管蛋白和FLT3，发现了一种具有强效抗肿瘤活性的新型1H-吡唑-3-胺衍生物6hPMID:日期:2026-11-15A novel series of 1H-pyrazole-3-amine derivatives was designed, synthesized, and their antitumor activities were evaluated. Among them, 6h showed potent antiproliferative activity against solid tumor cell lines and leukemia cell lines, with IC values ranging from 3.3 to 25.0 nM. Mechanism studies revealed that 6h could effectively inhibit microtubule polymerization (IC = 3.6 μM) via targeting the colchicine binding site and disrupted cellular microtubule networks. Notably, the preliminary kinase selectivity results showed 6h displayed selectivity for FLT3 kinase (IC = 58.6 nM) over other kinases screened, including the homologous c-KIT. Western blot analysis demonstrated that 6h inhibited the phosphorylation of FLT3 and its downstream signaling mediator STAT5 in MOLM-13 cells. 6h could induce tumor cell cycle arrest and apoptosis. Furthermore, in a MOLM-13 xenograft model, 6h at the dosage of 30 mg/kg exhibited effective antitumor activity without notable body-weight loss and the major organ damage. Pharmacokinetic evaluation of 6h in rats revealed an oral bioavailability of 5.6 %. Molecular docking and dynamics simulations supported stable binding modes of 6h with both tubulin and FLT3. Collectively, these results suggested that 6h could be regarded as a promising lead compound against tubulin and FLT3 for further investigation.
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9. Structural modification of imperatorin affords promising dual AhR/PDE4 modulators for anti-inflammatory therapy.
9. 欧前胡素的结构修饰提供了有前景的双重AhR/PDE4调节剂用于抗炎治疗PMID:日期:2026-11-15Precise and effective control of inflammation is critical for treating inflammatory diseases, highlighting an urgent clinical demand for improved anti-inflammatory agents. The aryl hydrocarbon receptor (AhR) is a key nuclear transcription factor in immune regulation, but clinically relevant AhR agonists such as Tapinarof show limited efficacyas monotherapy for psoriasis, resulting in frequent combination with PDE4 inhibitors in clinical practice to achieve optimal therapeutic outcomes because of the extensive crosstalk between AhR and PDE4 in inflammation. Our research group previously found that Imperatorin (Imp) is a natural AhR agonist with anti-inflammatory activity in vivo; however, its AhR agonist potency is far inferior to clinical candidates. Our research group previously found that Imperatorin is a natural AhR agonist with anti-inflammatory activity in vivo. Herein, we designed and synthesized a series of Imp derivatives to enhance AhR agonistic activity. The optimal compound T29 exhibited an EC of 0.11 μM in the HepG2-Lucia™ AhR assay. Moreover, T29 acted as a dual AhR/PDE4 modulator via the AhR-CYP1A1 and cAMP-PKA-CREB signaling pathways. In the imiquimod-induced psoriasis-like mouse model, T29 effectively alleviated epidermal hyperplasia and inflammatory infiltration and strongly inhibited IL-17A/F via topical administration. These findings identify T29 as a promising active dual-targeting anti-inflammatory agent worthy of further development.
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10. Design, synthesis, and biological activity of novel oxazole-based small molecule allosteric GLP-1R agonists.
PMID:日期:2026-11-15Glucagon-like peptide-1 receptor is a key target for type 2 diabetes, but current peptide agonists suffer from low oral bioavailability and poor adherence, highlighting the clinical significance of developing small-molecule modulators. Starting from the lead compound V-0219, a series of novel oxazole-containing small-molecule positive allosteric modulators of GLP-1R were designed and synthesized via a scaffold hopping strategy. Systematic structure-activity relationship studies led to the identification of compound 5b, which exhibited superior GLP-1R potentiating activity (44.8% at 10 μM) compared to the lead. Mechanistic studies demonstrated that 5b enhances GLP-1(7-36)- and GLP-1(9-36)-induced cAMP accumulation, directly binds to and stabilizes the GLP-1R protein, and exerts glucose-lowering effects in a GLP-1R-dependent manner. In oral glucose tolerance tests in hGLP-1R knock-in mice, 5b demonstrated modestly improved glucose-lowering efficacy compared to V-0219. In addition, 5b exhibited lower cytotoxicity, favorable metabolic stability in mouse liver microsomes and plasma, and acceptable oral exposure. Collectively, 5b, as a lead compound for orally available small-molecule GLP-1R modulators, warrants further investigation and holds promise for the treatment of type 2 diabetes and related metabolic disorders.