European Journal of Medicinal Chemistry最新文献

Discovery and preclinical evaluations of drug candidate DA-0157 capable of overcoming EGFR drug-resistant mutation C797S and EGFR/ALK co-mutations

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2025-01-25 DOI: 10.1016/j.ejmech.2025.117323

Peng He, Haiyan Li, Zhenyu Yang, Rui Zhang, Qijun Ye, Ta Deng, Wenwen Li, Shucheng He, Guangxin Dong, Zhou Yu, Yi Li

{"title":"Discovery and preclinical evaluations of drug candidate DA-0157 capable of overcoming EGFR drug-resistant mutation C797S and EGFR/ALK co-mutations","authors":"Peng He, Haiyan Li, Zhenyu Yang, Rui Zhang, Qijun Ye, Ta Deng, Wenwen Li, Shucheng He, Guangxin Dong, Zhou Yu, Yi Li","doi":"10.1016/j.ejmech.2025.117323","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117323","url":null,"abstract":"Activating mutations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are significant oncogenic drivers in non-small cell lung cancer (NSCLC) patients. Despite several approved EGFR and ALK inhibitors, drug-resistant mutations pose a major challenge. Especially, there is currently no approved EGFR inhibitors targeting the C797S mutation, a refractory mutation resistant to the third-generation EGFR inhibitors. Furthermore, an increasing number of patients with EGFR/ALK co-mutations have been identified in clinical practice, yet there are no effective therapeutic options available for them. In this study, we report the discovery and preclinical evaluations of a new small-molecule drug candidate, DA-0157, which is capable of overcoming EGFR drug-resistant mutation C797S and EGFR/ALK co-mutations. DA-0157 demonstrated excellent in vitro efficacy, significantly inhibiting various EGFRC797S mutants resistant to the third-generation EGFR inhibitors, ALK rearrangements, and EGFR/ALK co-mutations. In vivo studies revealed that DA-0157 substantially inhibited tumor growth in the LD1-0025-200717 EGFRDel19/T790M/C797S PDX model (40 mg/kg/d, TGI: 98.3%), Ba/F3-EML-4-ALK-L1196M CDX model (40mg /kg/d, TGI: 125.2%), and NCI-H1975 EGFRDel19/T790M/C797S & NCI-H3122 (EML4-ALK) dual-side implantation CDX model (40 mg/kg/d, TGI: 89.5% & 113.9%). DA-0157 demonstrates favorable pharmacokinetic properties and safety. Currently, DA-0157 (DAJH-1050766) is undergoing Phase I/II clinical trials.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"61 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031231","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}

引用次数: 0

Design, synthesis and structure-activity relationship of novel 1,2,4-triazolopyrimidin-5-one derivatives targeting GABAA1 and Nav1.2 with antiepileptic activity

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2025-01-25 DOI: 10.1016/j.ejmech.2025.117316

Tongtong Du, Jun Wu, Weina Wang, Wenhui Liang, Yunjie Li, Chuanlong Guo, Xiufen Li, Longjiang Huang, Haibo Yu

{"title":"Design, synthesis and structure-activity relationship of novel 1,2,4-triazolopyrimidin-5-one derivatives targeting GABAA1 and Nav1.2 with antiepileptic activity","authors":"Tongtong Du, Jun Wu, Weina Wang, Wenhui Liang, Yunjie Li, Chuanlong Guo, Xiufen Li, Longjiang Huang, Haibo Yu","doi":"10.1016/j.ejmech.2025.117316","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117316","url":null,"abstract":"A novel class of 7-phenyl-[1,2,4]triazol-5(4H)-one derivatives was designed and synthesized, and their in vivo anticonvulsant activities were evaluated using subcutaneous pentylenetetrazole (Sc-PTZ) and maximal electroshock (MES) tests. Compounds 3u, 4f and 4k exhibited significant anticonvulsant activities in the Sc-PTZ model with ED50 values of 23.7, 17.1 and 18.3 mg/kg, respectively. Neurotoxicity was accessed using the rotarod assay and none of the compounds demonstrated neurotoxicity at maximum solubility, with all TD50 values exceeding 267 mg/kg. This resulted in protective indexes (PI=TD50/ED50) values of greater than 11.3, 15.6 and 14.6, respectively. Compared to control drugs such as sodium phenytoin, sodium valproate, and carbamazepine, compounds 3u, 4f and 4k displayed superior anticonvulsant activities and reduced neurotoxicity. Mechanism results indicated that compounds 4k and 4f were sensitive to the subunit configuration of synaptic α1β2γ2 GABAA receptors, while compounds 3u and 4f dose-dependently reduced the peak amplitude of Nav1.2 currents. These structural compounds may provide a foundation for the further design of novel antiepileptic molecules with low neurotoxicity.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"15 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031227","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}

引用次数: 0

Antiproliferative Activity of Selenium-Enriched Coumarin Derivatives on the SK-N-SH Neuroblastoma Cell Line: Mechanistic Insights

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2025-01-25 DOI: 10.1016/j.ejmech.2025.117322

Ming Wang, Haoran Xu, Xuqiong Xiong, Linru Chang, Koutian Zhang, Yongnan Zhou, Feng Zhang, Annoor Awadasseid, Wen Zhang

{"title":"Antiproliferative Activity of Selenium-Enriched Coumarin Derivatives on the SK-N-SH Neuroblastoma Cell Line: Mechanistic Insights","authors":"Ming Wang, Haoran Xu, Xuqiong Xiong, Linru Chang, Koutian Zhang, Yongnan Zhou, Feng Zhang, Annoor Awadasseid, Wen Zhang","doi":"10.1016/j.ejmech.2025.117322","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117322","url":null,"abstract":"Thirty selenium-containing coumarin derivatives were synthesized and evaluated for inhibitory activity against 17 malignant tumor cell lines. Among these, compound 11i demonstrated the most potent inhibition of neuroblastoma SK-N-SH cells, with an IC50 of 2.5 ± 0.1 μM. Compound 11i notably inhibited SK-N-SH cell proliferation, migration, and invasion. Western blot and immunofluorescence analyses indicated that 11i increased the Bax/Bcl-2 protein expression ratio, promoted Cytochrome C release from mitochondria, and activated caspases 9 and 3, triggering the mitochondria-mediated apoptotic pathway and inducing endogenous tumor cell apoptosis. The compounds localized in the cytoplasm and co-localized with mitochondria, suggesting mitochondrial interaction and dysfunction. Computational docking studies revealed a strong binding affinity of 11i with Bcl-2 and mitochondrial G-quadruplexes. In a subcutaneous neuroblastoma-bearing mouse model, 11i showed notable anti-tumor efficacy with tumor inhibition rates of 79% (10 mg/kg) and 93% (20 mg/kg), exceeding that of cyclophosphamide. This study represents a novel finding on the anti-tumor activity of selenium-containing coumarin derivatives and provides a theoretical basis for developing coumarin-based therapeutics for neuroblastoma.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"40 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031228","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}

引用次数: 0

Discovery of the First Potent ROR1 Degrader for the Treatment of Non-Small Cell Lung Cancer

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2025-01-25 DOI: 10.1016/j.ejmech.2025.117325

Jinlin Li, Lin Li, Caiyun Hou, Zhaodi Tian, Yang Zhou, Jinwei Zhang, Xiaomei Ren, Zhen Wang, Weixue Huang, Ke Ding, Fengtao Zhou

{"title":"Discovery of the First Potent ROR1 Degrader for the Treatment of Non-Small Cell Lung Cancer","authors":"Jinlin Li, Lin Li, Caiyun Hou, Zhaodi Tian, Yang Zhou, Jinwei Zhang, Xiaomei Ren, Zhen Wang, Weixue Huang, Ke Ding, Fengtao Zhou","doi":"10.1016/j.ejmech.2025.117325","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117325","url":null,"abstract":"ROR1 has been identified as a pseudokinase, functioning as an allosteric regulator in tumor progression. Aberrant overexpression of ROR1 has been observed in various malignancies, highlighting its potential as therapeutic target for cancer therapy. Modulation of ROR1 by proteolysis targeting chimera degrader instead of traditional inhibitor could offer great efficiency in blocking its kinase-independent regulatory function. Here, we report the first potent ROR1 degraders constructed by connecting the E3 ligand to a ROR1 binder. One representative compound 11d exhibited remarkable efficacy in depleting ROR1 protein with a DC50 value of 40.88 nM and Dmax of 93.7%. Mechanistic investigations illuminated that compound 11d triggers ROR1 protein degradation in a ubiquitin proteasome system (UPS)-dependent manner. Additionally, compound 11d displayed a significantly enhanced ability to inhibit ROR1 signaling, induce apoptosis, and suppress proliferation in lung cell lines compared to the warhead ROR1 binder. These findings underscore the substantial potential of ROR1 degrader for the treatment of non-small cell lung cancer (NSCLC) cells.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"6 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031230","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}

引用次数: 0

Synthesis and biological evaluation of natural cleistanolate, its enantiomer and analogues

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2025-01-25 DOI: 10.1016/j.ejmech.2025.117326

Jelena Kesić, Mirjana Popsavin, Goran Benedeković, Vesna Kojić, Anita Bosak, Ana Matošević, Pavol Farkaš, Romana Madelová, Velimir Popsavin, Ivana Kovačević

引用次数: 0

Identification of Thieno[3,2-d]pyrimidine Derivatives as Potent and Selective Janus Kinase 1 Inhibitors

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2025-01-24 DOI: 10.1016/j.ejmech.2025.117308

Younghoon Kim, Eunhye Jeon, Hyunwoo Ahn, Juhee Kang, Taebo Sim

{"title":"Identification of Thieno[3,2-d]pyrimidine Derivatives as Potent and Selective Janus Kinase 1 Inhibitors","authors":"Younghoon Kim, Eunhye Jeon, Hyunwoo Ahn, Juhee Kang, Taebo Sim","doi":"10.1016/j.ejmech.2025.117308","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117308","url":null,"abstract":"Being a primary driver in oncogenic activations of JAK-STAT signaling pathway, Janus Kinase 1 (JAK1) stands out as a promising target in anti-cancer drug discovery. We employed a scaffold morphing strategy to design and synthesize thieno[3,2-d]pyrimidine derivatives, which led to identification of 24 as a potent and highly selective JAK1 inhibitor. Kinome-wide selectivity profiling reveals that 24 exhibits a high degree of selectivity for JAK1 among the 370 kinases tested. SAR study demonstrates that both 25 and 46, improved derivatives of 24, possess higher selectivity towards JAK1 over JAK2 and JAK3 compared to AZD4205 (9). It is of note that 46 has 4-fold higher enzymatic activity against JAK1 (IC50 = 0.022 μM) relative to 9. Moreover, both 25 and 46 demonstrate over 5-fold enhancement in anti-proliferative activities on NSCLC cells with regard to 9, accompanied by significant inhibition of JAK1 signaling. Compared with 9, derivative 24, 25, and 46 induce more strongly apoptosis, cell cycle arrest, and reduction of colony formation on NSCLC cells. Our findings offer valuable insights into the design of novel selective JAK1 inhibitors.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"38 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026986","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}

引用次数: 0

Rational design of dual-agonist peptides targeting GLP-1 and NPY2 receptors for regulating glucose homeostasis and body weight with minimal nausea and emesis

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2025-01-24 DOI: 10.1016/j.ejmech.2025.117320

Jing Liu, Weiwen Lu, Han Wu, Zhiming Yan, Yun Liu, Chunli Tang, Yangxin Chen, Shuang Wang, Weizhong Tang, Jing Han, Changhong Wei, Neng Jiang

{"title":"Rational design of dual-agonist peptides targeting GLP-1 and NPY2 receptors for regulating glucose homeostasis and body weight with minimal nausea and emesis","authors":"Jing Liu, Weiwen Lu, Han Wu, Zhiming Yan, Yun Liu, Chunli Tang, Yangxin Chen, Shuang Wang, Weizhong Tang, Jing Han, Changhong Wei, Neng Jiang","doi":"10.1016/j.ejmech.2025.117320","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117320","url":null,"abstract":"There is an urgent need for effective treatments targeting comorbidities of type 2 diabetes (T2DM) and obesity. Developing dual agonists of glucagon-like peptide 1 receptor (GLP-1R) and neuropeptide Y receptor type 2 (NPY2R) with combined PYY3-36 and GLP-1 bioactivity is promising. However, designing such dual agonists that effectively control glycemia and reduce weight while minimizing gastrointestinal side effects is challenging. In this study, we systematically evaluated the side effects induced by co-administering various GLP-1R agonists and PYY3-36 analogue. Our findings revealed that different GLP-1R agonist-PYY analogue combinations elicited gastrointestinal side effects of varying intensities. Among these, the co-administration of bullfrog GLP-1 analogue (bGLP-1) with PYY3-36 analogue resulted in lower gastrointestinal side effects. Thus, bGLP-1 was selected as the preferred candidate for designing dual GLP-1R/NPY2R agonists. Through stepwise structural design, optimization of linker arms, and durability enhancements, coupled with in vitro receptor screening, the novel peptide bGLP/PYY-19 emerged as the lead candidate. Notably, experimental results in mice and rats showed a significant reduction in emesis with bGLP/PYY-19 compared to semaglutide and bGLP-1 long-acting analogue (LAbGLP-1). Furthermore, bGLP/PYY-19 significantly outperformed semaglutide and LAbGLP-1 in reducing body weight in diet-induced obese (DIO) mice, without inducing nausea-associated behavior. These findings underscore the potential of dual-targeting single peptide conjugates as a promising strategy for developing glucoregulatory treatments that offer superior weight loss benefits and are better tolerated compared to treatments targeting GLP-1R alone.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"74 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026952","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}

引用次数: 0

SMARCA2 protein: structure, function and perspectives of drug design

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2025-01-24 DOI: 10.1016/j.ejmech.2025.117319

Zhaolin Guo, Peng Wang, Yuxuan Han, Sisi Jiang, Xinyu Yang, Shuang Cao

引用次数: 0

Recent advances in PKC inhibitor development: Structural design strategies and therapeutic applications

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2025-01-23 DOI: 10.1016/j.ejmech.2025.117290

Wen Li, Kun Zhu, Yuyin Liu, Meixi Liu, Qiu Chen

{"title":"Recent advances in PKC inhibitor development: Structural design strategies and therapeutic applications","authors":"Wen Li, Kun Zhu, Yuyin Liu, Meixi Liu, Qiu Chen","doi":"10.1016/j.ejmech.2025.117290","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117290","url":null,"abstract":"Protein kinase C (PKC) isozymes play critical roles in diverse cellular processes and are implicated in numerous diseases, including cancer, diabetes, and autoimmune disorders. Despite extensive research efforts spanning four decades, only one PKC inhibitor has received clinical approval, highlighting the challenges in developing selective and efficacious PKC-targeting therapeutics. Here we review recent advances in the development of small-molecule PKC inhibitors, focusing on structural design strategies, pharmacological activities, and structure-activity relationships. We analyze emerging approaches including fragment-based drug design, allosteric targeting, and natural product derivatization that have yielded promising new scaffold classes. Special attention is given to innovations in achieving isozyme selectivity, particularly for PKCα and PKCβ, which have proven crucial for therapeutic applications. We discuss how integration of computational methods, structural biology insights, and rational design principles has advanced our understanding of PKC inhibition mechanisms. This comprehensive analysis reveals key challenges in PKC drug development, including the need for enhanced selectivity and reduced off-target effects, while highlighting promising directions for future therapeutic development. Our findings provide a framework for designing next-generation PKC inhibitors with improved clinical potential.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"109 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026997","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}

引用次数: 0

Design, synthesis and evaluation of (E)-1-(4-(2-(1H-pyrazol-5-yl)vinyl)phenyl) derivatives as next generation selective RET inhibitors overcoming RET solvent front mutations (G810C/R)

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2025-01-23 DOI: 10.1016/j.ejmech.2025.117294

Mingjin Xu, Kaifu Wu, Rui He, Jiahuan He, Gangpeng Yang, Haowen Ma, Lijie Peng, Shuyao Zhang, Li Tan, Zhang Zhang, Qian Cai

{"title":"Design, synthesis and evaluation of (E)-1-(4-(2-(1H-pyrazol-5-yl)vinyl)phenyl) derivatives as next generation selective RET inhibitors overcoming RET solvent front mutations (G810C/R)","authors":"Mingjin Xu, Kaifu Wu, Rui He, Jiahuan He, Gangpeng Yang, Haowen Ma, Lijie Peng, Shuyao Zhang, Li Tan, Zhang Zhang, Qian Cai","doi":"10.1016/j.ejmech.2025.117294","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117294","url":null,"abstract":"RET is a well-recognized drug target for cancer treatment. Despite the promising efficacy of selective second-generation RET inhibitors Selpercatinib and Pralsetinib, the clinical benefits have been compromised due to the quickly developed resistance to these drugs. RET G810 mutations at the solvent front site have been identified as the major on-target mutations contributing to resistance against Selpercatinib and Pralsetinib. Therefore, there is an urgent need for the development of next-generation RET inhibitors to overcome acquired solvent-front resistance mutations. In this study, a series of (E)-1-(4-(2-(1H-pyrazol-5-yl)vinyl)phenyl) derivatives have been identified as selective next-generation RET inhibitors. The representative compound, CQ1373 exhibits potent cellular potency with IC50 values of 13.0, 25.7 and 28.4 nM against BaF3 cells expressing CCDC6-RET, CCDC6-RET-G810C and CCDC6-RET-G810R, respectively. A comprehensive selectivity profile across 89 kinases reveals that CQ1373 demonstrates good selectivity toward wild-type RET and solvent front mutants G810C/R with IC50 values of 4.2, 7.1 and 32.4 nM, respectively. Furthermore, western blot analysis reveals that CQ1373 effectively inhibits RET phosphorylation and downstream signaling through SHC. It also induces apoptosis and cell cycle arrest in a dose-dependent manner in BaF3 cells harboring CCDC6-RET, CCDC6-RET-G810C and CCDC6-RET-G810R fusions. More significantly, CQ1373 exhibits promising in vivo anti-tumor efficacy in a CCDC6-RET-G810R mice xenograft model, highlighting its potentials for RET-driven cancers treatment.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"51 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026984","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}

引用次数: 0