European Journal of Medicinal Chemistry最新文献

{"title":"Design, synthesis, and biological evaluation of novel pyridazinone-based EED inhibitors for prostate cancer","authors":"Zhang-Xu He, Shi-xuan Tan, Zengyangzong Dan, Guan-jun Dong, Yu-lin Liu, Li-Ying Ma, Wen Zhao","doi":"10.1016/j.ejmech.2025.117837","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117837","url":null,"abstract":"Aberrant activity of histone methyltransferase polycomb repressive complex 2 (PRC2) is associated with cancers and other diseases. Recently, compounds that bind to the EED subunit of PRC2 have emerged as allosteric inhibitors of PRC2, suggesting that targeting EED represents a novel strategy for human diseases. In this study, we designed and synthesized a new array of pyridazinone-based EED inhibitors derived from hit <strong>6</strong> identified through virtual screening, which was further optimized <em>via</em> extensive structure−activity relationship (SAR) studies. Ultimately, molecule <strong>39</strong> (IC₅₀= 0.62 μM) was identified as a potent EED inhibitor, which not only exhibited potent anti-proliferative activity and high selectivity against prostate cancer PC3 cells, but also could significantly suppress its colony formation and migration. Importantly, compound <strong>39</strong> showed acceptable PK properties and robust tumor regression in the PC3 xenograft model with the tumor growth inhibition reaching nearly 80%. Overall, our study identifies pyridazinone derivative <strong>39</strong> as a novel EED inhibitor, emerging as a promising lead compound warrant further optimization and development for prostate cancer.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"19 1","pages":"117837"},"PeriodicalIF":6.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252601","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}

{"title":"Novel trimethyl lock-based prostate-specific membrane antigen targeted Conjugates: Design, synthesis, and biological activity evaluation","authors":"Jiangzhu Zhan,&nbsp;Lijun Xu,&nbsp;Shuaibing Ding,&nbsp;Ning Ding,&nbsp;Wei Zhang","doi":"10.1016/j.ejmech.2025.117857","DOIUrl":"10.1016/j.ejmech.2025.117857","url":null,"abstract":"<div><div>Prostate cancer, a leading malignancy in men globally, faces challenges such as poor targeting, systemic toxicity, and drug resistance. This study developed an innovative multifunctional linker based on the trimethyl lock (TML) system, enabling parallel conjugation of key modules for targeted drug delivery. The linker integrates three functional components: (1) a targeting module (ACUPA), (2) a drug module (docetaxel, <strong>DTX</strong>), and (3) a trigger module (GSH-responsive disulfide bond). This “three-in-one” design allows flexible adjustment of physicochemical properties. Two conjugates were designed and formulated into nanoparticles. Physicochemical characterization demonstrated their excellent self-assembly and GSH-responsive release properties. Cellular assays showed that the conjugates exhibited comparable inhibitory activity against PSMA-positive 22Rv1 cells to <strong>DTX</strong>, while their activity against PSMA-negative PC 3 cells was lower. Cellular uptake confirmed higher internalization in 22Rv1 cells than in PC 3 cells. In vivo, low-dose <strong>PEG_3.4k-TML-DTX</strong> nanoparticles (10 mg/kg) achieved tumor inhibition rates similar to free <strong>DTX</strong> without causing weight loss, demonstrating favorable biosafety. This study provides a novel strategy for targeted chemotherapy with tumor microenvironment responsiveness and low toxicity.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117857"},"PeriodicalIF":6.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252599","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}

{"title":"Design of spiro-heterocyclic substituted diaminonaphthalene Keap1-Nrf2 protein-protein interaction inhibitors as novel anti-depressant agents","authors":"Yitong Chen ,&nbsp;Qingqing Qin ,&nbsp;Wenxin Ding ,&nbsp;Ruizhi Yu ,&nbsp;Rui Wang ,&nbsp;Hualong Ji ,&nbsp;Jianyu Yan ,&nbsp;Hao Ma ,&nbsp;Cheng-Shi Jiang ,&nbsp;Yi Sun ,&nbsp;Chunlin Zhuang","doi":"10.1016/j.ejmech.2025.117848","DOIUrl":"10.1016/j.ejmech.2025.117848","url":null,"abstract":"<div><div>Oxidative stress, inflammation and the Keap1-Nrf2 pathway are validated to be related to depression. Theoretically, modulating Keap1 and Nrf2 protein-protein interaction (PPI) should be an effective method to activate Nrf2 for the treatment of major depressive disorders. We previously reported NXPZ-2, a 1,4-diaminonaphthalene, as a Keap1-Nrf2 PPI inhibitor that exhibited promising effects in an Alzheimer's disease (AD) mouse model. However, its pharmacokinetic properties were limited. Herein, we, for the first time, developed a series of heterocyclic substituted diaminonaphthalenes by an “Escape from Flatland” strategy to improve sp³ hybridized carbons. These compounds exhibited strong binding affinity for Keap1. A crystallographic analysis revealed the high-resolution (1.44 Å) binding of <strong>CD-10</strong> with the Keap1 protein, elucidating the complexity of <strong>CD-10</strong>'s binding mechanism. In an LPS-stimulated BV2 cell model, <strong>CD-10</strong> demonstrated the best anti-oxidative stress and anti-inflammatory potential. Furthermore, <strong>CD-10</strong>'s ability to penetrate the blood-brain barrier has been significantly improved. In a chronic unpredictable mild stress (CUMS) mouse model, treatment with <strong>CD-10</strong> effectively alleviated anxiety and depressive behaviors and restored serum neurotransmitter levels by promoting Nrf2 nuclear translocation. Overall, our findings validate that the Keap1-Nrf2 PPI inhibitor holds promise as a preclinical candidate for the treatment of depression.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117848"},"PeriodicalIF":6.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237459","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}

{"title":"Novel water-soluble and highly efficient dual type I/II next generation inhibitors of FMS-like tyrosine kinase 3 (FLT3)","authors":"Andreas Sellmer ,&nbsp;Marina Able ,&nbsp;Karsten Spiekermann ,&nbsp;Maria Reinecke ,&nbsp;Bernhard Kuster ,&nbsp;Kirsten Utpatel ,&nbsp;Lukas Wirth ,&nbsp;Herwig Pongratz ,&nbsp;Nicole Plank ,&nbsp;Pierre Koch ,&nbsp;Sigurd Elz ,&nbsp;Amrei Fischer ,&nbsp;Belay Tizazu ,&nbsp;Heinz-Herbert Fiebig ,&nbsp;Stefan Dove ,&nbsp;Siavosh Mahboobi","doi":"10.1016/j.ejmech.2025.117849","DOIUrl":"10.1016/j.ejmech.2025.117849","url":null,"abstract":"<div><div>Mutations of the FMS-like tyrosine kinase (FLT3) occur in acute myeloid leukemia (AML) and are associated with very poor prognosis. Available FLT3 inhibitors are potent but either show a lack of selectivity regarding other tyrosine kinases or only transient efficacy due to emerging resistance under therapy. Water-soluble derivatives of the tyrosine kinase inhibitor Marbotinib are highly selective dual-type I/II inhibitors of FLT3.</div><div>The bisarylmethanone-based compound <strong>29</strong> and its carbamate derivative <strong>42</strong> show excellent results in various biological tests. They inhibit FLT3-ITD (internal tandem duplication) as well as therapy-associated FLT3-TKD point mutations. Additionally, good water solubility and consequently biological availability was achieved by attaching amine functions to appropriate scaffold positions, suggested by modeling of inhibitor binding at inactive and active FLT3 states. Subsequent formation of different salts led to very promising results in <em>in vivo</em> studies and improvements compared to midostaurin (<strong>1b</strong>), Quizartinib (<strong>7</strong>), Marbotinib <strong>10</strong> and its carbamate <strong>11c</strong>.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117849"},"PeriodicalIF":6.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237458","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}

{"title":"NQO1 Induction and Radiation-Based Biodistribution Study of a New Quinoline Derivative Identified in a Screen of 6,8-Diiodoquinazolinone Sulfonamide Conjugates","authors":"Aiten M. Soliman, Mostafa M. Ghorab, Maureen Higgins, Albena T. Dinkova-Kostova, Mohamed Korany, Mohamed A. Amin, Mohammed A. Khedr, Tamer M. sakr","doi":"10.1016/j.ejmech.2025.117855","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117855","url":null,"abstract":"A series of quinazoline derivatives <strong>10–23</strong> incorporating benzenesulfonamide and various aliphatic, aromatic and heterocyclic acetamide tails were designed, synthesized, and <em>in vitro</em> evaluated for their ability to activate nuclear factor erythroid 2-related factor 2 (Nrf2) using its classical target NAD(P)H: quinone oxidoreductase 1 (NQO1) in Hepa1c1c7 murine hepatoma cells. Compounds <strong>13</strong> and <strong>20</strong> exhibited the highest potency among this series, with CD values 14 and 3 μM, respectively. The quinoline derivative <strong>20</strong> was subjected to radiolabeling. The radio-synthesized derivative was assessed for its biodistribution in normal and tumor-bearing animal models, where it displayed high <em>in vivo</em> stability and selectivity toward tumor cells. Molecular docking of <strong>20</strong> within the Nrf2-binding site of Kelch-like ECH-associated protein 1 (Keap1) predicted the highest binding affinity –<strong>8.76 Kcal/mol</strong> with the least RMSD value 1.01 Å. It showed a stable binding confirmed by RMSF compared to the co-crystallized ligand. This study identifies compound <strong>20</strong> as a promising antioxidant for continued optimization in redox-modulating research.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"61 1","pages":"117855"},"PeriodicalIF":6.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237460","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}

{"title":"Syntheses of benzothiazole amidoximes and arylimidamides and evaluation of their ADME and DNA binding properties and activity against Trypanosoma brucei","authors":"Valentina Rep Kaulić ,&nbsp;Martina Piškor ,&nbsp;Sanja Koštrun ,&nbsp;Astrid Milić ,&nbsp;Marijana Radić Stojković ,&nbsp;Amanda Fortes Francisco ,&nbsp;Martin C. Taylor ,&nbsp;John M. Kelly ,&nbsp;Silvana Raić-Malić","doi":"10.1016/j.ejmech.2025.117854","DOIUrl":"10.1016/j.ejmech.2025.117854","url":null,"abstract":"<div><div>Novel 6-amidoxime- and 6-arylimidamide-substituted benzothiazoles were synthesised to investigate their activity against <em>Trypanosoma brucei,</em> the causative agent of African trypanosomiasis. Benzothiazole amidoxime <strong>12b</strong>, with diethylaminoethyl and fluorine substituents on a phenoxymethylene linker exhibited pronounced (IC₅₀ = 0.92 μM) and selective (SI = 18) antitrypanosomal activity. ADME profiling showed that the majority of compounds synthesised are metabolically stable and that arylimidamides have low membrane permeability, while amidoximes, including <strong>12b</strong>, have moderate to high permeability. Binding assays indicate that amidoxime <strong>12b</strong> binds to DNA/RNA by intercalation, whereas arylimidamide <strong>29b</strong> displays groove binding. <strong>12b</strong> was found to be a substrate of the P-glycoprotein efflux pump, a factor that may have limited its activity in a murine model of infection, despite the other favourable properties. Structural diversification of aryl-substituted motif in amidoxime benzothiazole series will be explored to further optimize activity and ADME properties, and to overcome issues associated with low membrane permeability.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117854"},"PeriodicalIF":6.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237026","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}

{"title":"Heterocyclic androstane derivatives targeting hormone-related cancers: Synthesis, bioactivity and docking studies","authors":"Tijana Lj. Šestić ,&nbsp;Sofija S. Bekić ,&nbsp;Maja A. Marinović ,&nbsp;Marie Kvasnicová ,&nbsp;Tereza Štenclová ,&nbsp;Lucie Rárová ,&nbsp;Andjelka S. Ćelić ,&nbsp;Edward T. Petri ,&nbsp;Jovana J. Ajduković ,&nbsp;Miroslav Strnad ,&nbsp;Marina P. Savić","doi":"10.1016/j.ejmech.2025.117850","DOIUrl":"10.1016/j.ejmech.2025.117850","url":null,"abstract":"<div><div>Insertion of a heterocyclic ring into the steroid core could enhance bioactivity, improve selectivity and reduce side effects in potential drugs for cancer therapy. The present study describes the synthesis of new thiazoline, thiadiazoline and thiazolidinone steroid compounds combined with lactone, lactam or pyridine moieties. These steroid hybrid molecules may be potential candidates for drug design, with improved biological activity and bioavailability. The starting androstenedione or dehydroepiandrosterone were modified by multiphase synthesis into thiosemicarbazone androstane derivatives, direct precursors for the synthesis of new heterocyclic compounds. Their cytotoxicity was tested against five cancer cell lines: breast adenocarcinoma cells (MCF7), acute lymphoblastic leukemia (CCRF-CEM), cervical carcinoma cells (HeLa), hormone-independent (DU 145) and hormone-sensitive prostate cancer cells (LNCaP), as well as against normal skin fibroblasts (BJ). Compounds <strong>5</strong> and <strong>16</strong> were found to be the most selective, with both inducing apoptosis in HeLa cells. New compounds were also evaluated for their relative binding affinities for the ligand-binding domains (LBDs) of estrogen receptor α (ERα), estrogen receptor β (ERβ), androgen receptor (AR) or glucocorticoid receptor (GR) using a fluorescent assay in yeast cells, where thiazole derivative <strong>13</strong> exhibited the highest binding affinity for ERα, while thiazolidinone <strong>7</strong> showed strong selective affinity for ERβ. Furthermore, inhibition potential against human aldo-keto reductase 1C3 and 1C4 (AKR1C3 and AKR1C4) was evaluated by fluorescence spectroscopy, with acetamido thiadiazoline <strong>21</strong> displaying an IC₅₀ value for AKR1C3 slightly higher than the reference inhibitor ibuprofen. Molecular docking studies were used to propose protein-ligand binding models for compounds showing the strongest affinity toward specific proteins based on <em>in vitro</em> experiments. In summary, our results suggest that the tested heterocyclic derivatives are active against hormone-dependent cancer cells and represent promising leads for the development of novel therapeutics.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117850"},"PeriodicalIF":6.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144229249","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}

{"title":"Corrigendum to “Design, synthesis, and biological evaluation of novel BTK-targeting proteolysis targeting chimeras (PROTACs) with enhanced pharmacokinetic properties” [Eur. J. Med. Chem. 289 (2025) 117420]","authors":"Ying Lin ,&nbsp;Jing Liu ,&nbsp;Xinjian Tian ,&nbsp;Jin Wang ,&nbsp;Huahua Su ,&nbsp;Jianpin Xiang ,&nbsp;Tao Cao ,&nbsp;Yonghui Wang ,&nbsp;Qiong Xie ,&nbsp;Xufen Yu","doi":"10.1016/j.ejmech.2025.117828","DOIUrl":"10.1016/j.ejmech.2025.117828","url":null,"abstract":"","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117828"},"PeriodicalIF":6.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211494","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}

{"title":"Indo–Gem: An activatable theranostic prodrug, a “Turn–On” fluorescent probe, and a targetable imaging agent in the zebrafish gallbladder system","authors":"Neha Jain ,&nbsp;Arkaprava Roychaudhury ,&nbsp;JunHyuk Kim ,&nbsp;Ruchi Dixit ,&nbsp;Prasad M. Sonawane ,&nbsp;Michio Iwaoka ,&nbsp;Cheol-Hee Kim ,&nbsp;Satish Balasaheb Nimse ,&nbsp;David G. Churchill","doi":"10.1016/j.ejmech.2025.117836","DOIUrl":"10.1016/j.ejmech.2025.117836","url":null,"abstract":"<div><div>Theranostics are crucial in both cancer diagnosis and targeted drug delivery, as they enable the simultaneous detection and treatment of disease within a single molecular or conjugated platform. However, theranostics is still facing challenges like real-time tracking for “where” prodrugs are activated <em>in vivo</em>, which poses a significant problem for molecule development. Organ-specific action to inspire the creation of innovative disease–curing technologies that are both accurate and efficient is still an underestimated task. We herein showcase the novel serendipitous gallbladder–targeting indole–based prodrug <strong>Indo–Gem</strong> for precise imaging-guided cancer therapy. <strong>Indo–Gem</strong> was prepared by an indole–malononitrile (dye) moiety, attached to the selected parent drug Gemcitabine via a disulfide cleavable linker. <strong>Indo–Gem</strong> is triggered by DTT with 27–fold fluorescent enhancement at pH 7.4, registering within 21 min. Unlike the most ignored adverse effects in prodrug activation, this indole–based dye targeting in a specific organ region of a zebrafish model via a combination of imaging ability and drug release. This is the first case that employs an indole–based moiety in prodrug design without any use of targeting ligands; the profound success of <strong>Indo–Gem</strong> and the well–defined mechanism suggest that the indole might serve as a scaffold to create novel therapeutic prodrugs with improved drug potency in future drug development.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117836"},"PeriodicalIF":6.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211489","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}

{"title":"A medicinal chemistry perspective on ATR: Current status and future directions","authors":"Kun Li ,&nbsp;Xiangxi Sun ,&nbsp;Shengyu Liu ,&nbsp;Yidong Liu ,&nbsp;Xue Feng ,&nbsp;Guogang Zhang","doi":"10.1016/j.ejmech.2025.117834","DOIUrl":"10.1016/j.ejmech.2025.117834","url":null,"abstract":"<div><div>ATR (Ataxia Telangiectasia and Rad3-related) is a serine/threonine protein kinase that plays a critical role in DNA replication stress response. Based on the mechanism of “synthetic lethality” and their radiosensitizing/chemosensitizing properties, ATR inhibitors have become a popular target for drug design. Currently, several ATR inhibitors have entered clinical trials and shown promising potential in cancer treatment. However, the clinical efficacy and safety of ATR inhibitors in different cancers remain issues that cannot be overlooked. This review summarizes the protein structure and biological functions of ATR, along with its mechanisms in combination therapies. We highlight the design strategies, structure−activity relationships, and biological activity assessments of ATR inhibitors. Finally, this review endeavors to provide a comprehensive perspective on the evolving field of ATR-targeted drug discovery, offering valuable insights for future drug development.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117834"},"PeriodicalIF":6.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201497","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}