European Journal of Medicinal Chemistry最新文献

{"title":"An overview of KRAS G12D inhibitors: Expanding the therapeutic frontier of KRAS in targeting KRAS G12D using diverse therapeutic modalities","authors":"Varun Kumar, Abhinandan K. Danodia, Pradeep S. Jadhavar, Subhendu K. Mohanty, Swapan K. Samanta","doi":"10.1016/j.ejmech.2025.118555","DOIUrl":"10.1016/j.ejmech.2025.118555","url":null,"abstract":"","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118555"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920571","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, synthesis, and evaluation of unsymmetrical trifluoromethyl-containing bisindolylmethane derivatives inducing endoplasmic reticulum stress in human lung adenocarcinoma","authors":"Wenrun Zhu ,&nbsp;Jun Huang ,&nbsp;Xiaoyi Deng ,&nbsp;Yichuan Chen ,&nbsp;Lianbao Ye ,&nbsp;Shuang Tian ,&nbsp;Lin Zhou ,&nbsp;Jiang Weng ,&nbsp;Yunjun Liu","doi":"10.1016/j.ejmech.2026.118564","DOIUrl":"10.1016/j.ejmech.2026.118564","url":null,"abstract":"<div><div>Bisindolylmethane (<strong>BIM</strong>) is an important alkaloid derived from cruciferous plants that exhibits anti-cancer biological activity. Molecules with a <strong>BIM</strong> skeleton have long been widely recognized by medicinal chemists. Unfortunately, due to limitations in synthetic methods, research on this skeleton has mainly focused on symmetrical 3,3′-bisindolylmethane derivatives (3,3′-<strong>BIMs</strong>), wherein the two indole rings possess identical structures. In contrast, research on unsymmetrical 3,3′-<strong>BIMs</strong> has progressed slowly. Meanwhile, trifluoromethyl is a widely used “star group” in drug design due to its ability to improve pharmacological and pharmaceutical properties. To discover novel <strong>BIMs</strong> with significant anti-cancer potential and to study the variety of their structures, we designed and synthesized a series of unsymmetrical trifluoromethyl-containing <strong>BIMs</strong> based on previously reported S_N1-type dehydrative nucleophilic substitution by our group. These novel <strong>BIMs</strong> inhibit various cancer cells, especially lung cancer cells A549. Among them, the compound <strong>5b</strong> effectively induces endoplasmic reticulum stress (ERS) and leads to apoptosis, demonstrating outstanding anti-non-small cell lung cancer (NSCLC) effects in vitro and in vivo, and was significantly more effective than the <strong>BIM</strong> group. The IC₅₀ values of <strong>BIM</strong> and <strong>5b</strong> against A549 cells are 54.76 ± 4.7 μM and 3.88 ± 0.1 μM, respectively. Specifically, anti-tumor activity assays in vivo found the inhibitory rates of 34.80 % for <strong>BIM</strong> and 80.32 % for <strong>5b</strong>. Hematoxylin-eosin (H&amp;E) results showed that <strong>5b</strong> does not cause chronic organ damage. Clearly, <strong>5b</strong> greatly enhances anti-cancer efficacy, effectively restraining cell colonies and proliferation in the S phase. Additionally, <strong>5b</strong> increases the content of reactive oxygen species (ROS), causing a decline in the mitochondrial membrane potential and promoting Ca²⁺ release. Further studies on the mechanism revealed that <strong>5b</strong> induces ERS by activating the PERK-elF2α-CHOP signaling pathway, which could further regulate caspase and Bcl-2 family proteins, leading to apoptosis. These results demonstrate that <strong>5b</strong> may be potent anticancer candidates for A549 tumor.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118564"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947735","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":"Dual / bifunctional targeting of bromodomain and extra-terminal (BET) proteins: Expanding the paradigm of epigenetic drug discovery","authors":"Fei Jiang ,&nbsp;Huili Li ,&nbsp;Quan Sun ,&nbsp;Jiandong Huang ,&nbsp;Xianggui Chen ,&nbsp;Qian Liang ,&nbsp;Xueyuan Luo ,&nbsp;Wenbao Zhang ,&nbsp;Dandan He ,&nbsp;Xiangchun Shen","doi":"10.1016/j.ejmech.2025.118524","DOIUrl":"10.1016/j.ejmech.2025.118524","url":null,"abstract":"<div><div>Bromodomain and extra-terminal (BET) proteins function as key epigenetic regulators of oncogenic, inflammation, and immune pathways, however, their therapeutic targeting has been constrained by limitations of monofunctional inhibitors—notably compensatory resistance, narrow therapeutic indexes, and context-specific efficacy. This review delineates a paradigm shift from occupancy-based inhibition toward multidimensional bifunctional engagement, overcoming these barriers through rationally designed dual-target inhibitors (e.g., BET/HDAC, BET/kinases), catalytic degraders (PROTACs, molecular glues), and pathway-directed systems (autophagy-lysosome modulators, apoptotic reactivators, RIPTACs, and TCIPs). Advanced delivery platforms, including antibody–drug conjugates (ADCs) and stimuli-responsive nanocarriers, may enhance spatiotemporal precision and reduce systemic toxicity. By exploiting synergistic epigenetic-kinase cooperativity or leveraging ternary complex-driven degradation, these innovations are redefining the pharmacological landscape for BET proteins. Collectively, such strategies may provide durable efficacy against recalcitrant cancers, inflammatory disorders, and neurodegenerative diseases, suggesting emerging new design principles for epigenetic therapeutics.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118524"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895303","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 novel RANKL-targeted selenyl quinolinamide alleviates ovariectomy-induced bone loss through inhibiting ROS, MAPK and NF-κB signaling pathways","authors":"Lele Yi ,&nbsp;Yifan Ping ,&nbsp;Xiaolong Ye ,&nbsp;Shaoli Wang ,&nbsp;Yao Wu ,&nbsp;Lingling Zhou ,&nbsp;Xiangrui Song ,&nbsp;Haojin Chen ,&nbsp;Bin Li ,&nbsp;Yixin Mao ,&nbsp;Yang Chen ,&nbsp;Zhihao Yu ,&nbsp;Weiwei Xue ,&nbsp;Jing Wang ,&nbsp;Shengbin Huang ,&nbsp;Zengqiang Song","doi":"10.1016/j.ejmech.2025.118533","DOIUrl":"10.1016/j.ejmech.2025.118533","url":null,"abstract":"<div><div>The osteoclast is the only bone cell responsible for bone resorption, intracellular reactive oxygen species (ROS) are key signaling factors that regulate RANKL-induced osteoclast differentiation. Organoselenium compounds have been demonstrated with good antioxidant activity by scavenging ROS. However, these compounds exerting anti-osteoclastogenesis activity by reducing ROS levels have not been reported. In this study, a series of selenyl quinolinamides were synthesized using a novel, simple, and metal-free method at room temperature, and their osteoclastogenesis inhibitory effects <em>in vitro</em> were tested. The most promising compound <strong>3w</strong> with an <em>IC</em>₅₀ value of 0.577 μM, markedly inhibited RANKL-induced osteoclast formation, bone resorption, and osteoclast-specific genes and proteins expressions <em>in vitro</em>. Additionally, <strong>3w</strong> suppressed RANKL-stimulated intracellular ROS levels by inhibition of ROS production and promotion of ROS scavenging, and inhibited downstream MAPK and NF-κB signaling pathways. <em>In vivo</em>, <strong>3w</strong> significantly prevented bone loss in ovariectomized osteoporosis mice. Moreover, <strong>3w</strong> could bind to RANKL and interfere with RANKL-RANK interaction. Our findings may offer a valuable direction for the development of novel organoselenium-based antiosteoporosis agents.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118533"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895280","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":"Discovery of quaternary ammonium compounds with broad antibacterial activity and efficacy in S. aureus infection model","authors":"Akash Shinde ,&nbsp;Deepanshi Saxena ,&nbsp;Rahul Maitra ,&nbsp;Swechchha Singh ,&nbsp;Abdul Akhir ,&nbsp;Shivani Maykalwar ,&nbsp;Kranthi Gupta ,&nbsp;B. Angayarkanni ,&nbsp;Karnati Sai Pranathi ,&nbsp;Sunil Misra ,&nbsp;Vijayan N. Azger Dusthackeer ,&nbsp;Jagadeesh Babu Nanubolu ,&nbsp;Sidharth Chopra ,&nbsp;Haridas B. Rode","doi":"10.1016/j.ejmech.2025.118491","DOIUrl":"10.1016/j.ejmech.2025.118491","url":null,"abstract":"<div><div>Antimicrobial resistance (AMR) has become a significant global health concern, contributing heavily to the morbidity and mortality associated with both hospital-acquired (nosocomial) and community-acquired infections. In this context, we investigated the antibacterial potential of quinoline-based quaternary ammonium compounds (QACs) against Gram-positive bacteria, including multidrug-resistant (MDR) strains. Compound <strong>20</strong> was identified through a detail Structure-Activity-Relationship study and demonstrated strong antibacterial potential with an MIC of 0.125 μg/mL against <em>S. aureus</em>. This compound is effective against clinical MDR-MRSA and VRSA. Of note, <strong>20</strong> effectively inhibited bacterial growth in both planktonic and biofilm forms in a concentration-dependent manner. It's favorable toxicity profile (SI 72 w.r.t. CHO–K1 cells, HC₅₀ of &gt;100 μg/mL against human RBC) and prolonged post-antibiotic effect (PAE) compared to vancomycin highlights its potency as a safe therapeutic agent. Notably, the compound's <em>in vitro</em> efficacy was successfully translated <em>in vivo</em>, supporting its potential for development into a novel treatment for drug-resistant <em>S. aureus</em> infections, particularly for topical applications.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118491"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796174","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 synthesis and biological evaluation of novel BCL6/GSPT1 degrader as anti-DLBCL agent","authors":"Rong Hu ,&nbsp;Xia-Tong Hu ,&nbsp;Ying-Yue Yang ,&nbsp;Ling-Feng Du ,&nbsp;Xiong-Xiong Lan ,&nbsp;Peng Luo ,&nbsp;Cai-Hua Li ,&nbsp;Luo-Ting Yu ,&nbsp;Ning-Yu Wang","doi":"10.1016/j.ejmech.2026.118567","DOIUrl":"10.1016/j.ejmech.2026.118567","url":null,"abstract":"<div><div>BCL6 is regarded as a promising therapeutic target for diffuse large B-cell lymphoma. However, most of the current BCL6 inhibitors and degraders have demonstrated limited antitumor efficacy when used as monotherapy. We hypothesized that developing multitarget degraders capable of simultaneously degrading multiple lymphoma-driving proteins might yield superior anti lymphoma activity. In this study, based on the BCL6 inhibitor <strong>BI3812</strong>, we designed and identified a dual-target degrader <strong>A5</strong>, which effectively degraded both BCL6 and GSPT1. <strong>A5</strong> induced the degradation of BCL6 and GSPT1 in a time- and concentration-dependent manner, restored the expression of BCL6-regulated genes, and significantly promoted DNA damage in Farage cells. Consequently, <strong>A5</strong> exhibited enhanced antiproliferative activity compared to the BCL6 inhibitor <strong>BI3812</strong> and the BCL6 degrader <strong>BI3802</strong>, along with induction of cell cycle arrest and apoptosis. Furthermore, <strong>A5</strong> significantly downregulated BCL6 and GSPT1 protein levels in vivo. Thus, this study provides a solid foundation for the development of novel multitarget BCL6 degraders with improved anti-lymphoma potential.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118567"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947736","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":"Discovery of WWZ-11-098: a rigid and selective CDK6 degrader","authors":"Wanwan Zhang ,&nbsp;Jinfeng Wen ,&nbsp;Yuanyuan Wu ,&nbsp;Yong Xuan ,&nbsp;Qiangqiang Han ,&nbsp;Xi Chen ,&nbsp;Jingtian Yu ,&nbsp;Haijun Yu ,&nbsp;Baishan Jiang","doi":"10.1016/j.ejmech.2026.118569","DOIUrl":"10.1016/j.ejmech.2026.118569","url":null,"abstract":"<div><div>Dysregulation of the cell cycle, a hallmark of cancer, frequently involves aberrant activation of cyclin D-CDK4/6 complexes. Although dual-CDK4/6 inhibitors are effective in advanced hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, CDK6 is preferentially expressed and functionally upregulated in hematologic malignancies, making it a promising therapeutic target. The high structural homology between CDK4 and CDK6, however, has made developing selective CDK6 inhibitors exceptionally difficult. Herein, we report the design and synthesis of a novel series of CDK6 degraders based on a CDK2/4/6 inhibitor. This investigation led to the discovery of a CDK6 degrader <strong>WWZ-11</strong>–<strong>098</strong>. <strong>WWZ-11</strong>–<strong>098</strong> induced pronounced CDK6 degradation (DC₅₀ = 2.6 nM and D_max &gt;99 %) in a Cereblon (CRBN)-dependent manner, while sparing CDK1, CDK2, CDK4, and CDK9. Moreover, <strong>WWZ-11</strong>–<strong>098</strong> exhibited potent antiproliferation activity (MOLT-4: IC₅₀ = 70 nM) by inducing G1-S cell cycle arrest. In addition, <strong>WWZ-11</strong>–<strong>098</strong> displayed favorable pharmacokinetic properties (C_max = 11833 ng/mL, T_1/2 = 2.64 h after a 5 mpk IV dose) and exhibited robust antitumor efficacy (TGI: 77.1 % @10 mpk) in a MOLT-4 xenograft model without signs of toxicity. The compound provides not only a valuable chemical probe but also a lead structure for further development of CDK6 degraders.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118569"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956874","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 “Impact of site-specific conjugation strategies on the pharmacokinetics of antibody-conjugated radiotherapeutics” [Eur J Med Chem. 2024 Dec 15; 280:116927. doi: 10.1016/j.ejmech.2024.116927. PMID: 39378827]","authors":"Ábel Nagy ,&nbsp;David Ulmert ,&nbsp;Wahed Zedan ,&nbsp;Claire M. Storey ,&nbsp;Julie Park ,&nbsp;Susanne Geres ,&nbsp;Katharina Lückerath ,&nbsp;Kjell Sjöström ,&nbsp;Hadis Westin ,&nbsp;Norbert Peekhaus ,&nbsp;Daniel LJ. Thorek ,&nbsp;Amelie Eriksson Karlström ,&nbsp;Mohamed Altai","doi":"10.1016/j.ejmech.2026.118589","DOIUrl":"10.1016/j.ejmech.2026.118589","url":null,"abstract":"","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118589"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008347","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":"Small-molecule fluorescent probes for the aminergic GPCRs – What new tool compounds do we have post-2014 and what can they do?","authors":"Christopher Zi Qian Choo,&nbsp;Joey Yun Xuan Ching,&nbsp;Myra Mazhar Ud Deen,&nbsp;Zhi Yuan Kok","doi":"10.1016/j.ejmech.2026.118579","DOIUrl":"10.1016/j.ejmech.2026.118579","url":null,"abstract":"<div><div>Aminergic G protein-coupled receptors (GPCRs) are heavily involved in the physiological functions of the human body and represent prominent drug targets for numerous diseases. Despite extensive work over the years, knowledge gaps persist as not all aminergic GPCRs are currently drugged. This gap could be addressed by using small-molecule fluorescent probes across a range of assay formats and experiments to obtain deeper insights into the molecular pharmacology of these receptors. This review highlights key developments from 2014 to 2024 in the design and application of fluorescent probes targeting aminergic GPCRs, featuring a total of 36 fluorescent probes spanning all prominent aminergic GPCR subfamilies: adrenergic, dopaminergic, histaminergic, muscarinic, and serotonergic receptors. This review provides a detailed overview of the approaches to probe design, their pharmacological profiles and their reported utilities in ligand binding assays and imaging studies. In recent years, these applications have expanded to include <em>ex vivo</em> and <em>in vivo</em> studies in both mice and human tissue models. With the integration of cutting-edge image processing and artificial intelligence-driven image recognition technologies, fluorescent probes will remain indispensable tools for investigating the molecular pharmacology of aminergic GPCRs, playing a crucial role in driving forward drug discovery in this field.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118579"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995779","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":"Small-molecule drug discovery targeting the orphan G protein-coupled receptor GPR84 as potential therapeutics","authors":"Binghan Xue ,&nbsp;Yao Xiao ,&nbsp;Weipeng Hu ,&nbsp;Fangli Zhou ,&nbsp;Bowen Zhang ,&nbsp;Yiwen Zhang","doi":"10.1016/j.ejmech.2026.118561","DOIUrl":"10.1016/j.ejmech.2026.118561","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118561"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897661","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}