Oluwatosin A. Obisesan, Samuel Ofori, Owamagbe N. Orobator, Himanshi Sharma, Emma Groetecke, Samuel G. Awuah
{"title":"Discovery of a Pyrazolopyridinone-Based MYC Inhibitor That Selectively Engages Intracellular c-MYC and Disrupts MYC–MAX Heterodimerization","authors":"Oluwatosin A. Obisesan, Samuel Ofori, Owamagbe N. Orobator, Himanshi Sharma, Emma Groetecke, Samuel G. Awuah","doi":"10.1021/acs.jmedchem.4c02556","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c02556","url":null,"abstract":"c-MYC is an oncogenic transcription factor that plays a crucial role in the regulation of downstream targets involved in proliferation, apoptosis, differentiation, metabolism, signaling, and immune response processes whose deregulation leads to the progression of different pathologies. The development of selective and potent small-molecule inhibitors of c-MYC remains a grand challenge in chemical biology and medicine due to its undruggability, derived from extensive intrinsic disorder. In this study, we identified a novel dihydro pyrazolo pyridinone scaffold, <b>MY05</b>, that selectively targets c-MYC in cells and disrupts MYC–MAX interaction. MY05 engages intracellular c-MYC, modulates c-MYC thermal stability, reduces c-MYC transcriptional targets, and inhibits proliferation in cancer cells and tumor growth in mice. In summary, we identified a novel compound that directly interacts with c-MYC to disrupt the transcriptional program.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"87 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oluwatosin A. Obisesan, Samuel Ofori, Owamagbe N. Orobator, Himanshi Sharma, Emma Groetecke and Samuel G. Awuah*,
{"title":"Discovery of a Pyrazolopyridinone-Based MYC Inhibitor That Selectively Engages Intracellular c-MYC and Disrupts MYC–MAX Heterodimerization","authors":"Oluwatosin A. Obisesan, Samuel Ofori, Owamagbe N. Orobator, Himanshi Sharma, Emma Groetecke and Samuel G. Awuah*, ","doi":"10.1021/acs.jmedchem.4c0255610.1021/acs.jmedchem.4c02556","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c02556https://doi.org/10.1021/acs.jmedchem.4c02556","url":null,"abstract":"<p >c-MYC is an oncogenic transcription factor that plays a crucial role in the regulation of downstream targets involved in proliferation, apoptosis, differentiation, metabolism, signaling, and immune response processes whose deregulation leads to the progression of different pathologies. The development of selective and potent small-molecule inhibitors of c-MYC remains a grand challenge in chemical biology and medicine due to its undruggability, derived from extensive intrinsic disorder. In this study, we identified a novel dihydro pyrazolo pyridinone scaffold, <b>MY05</b>, that selectively targets c-MYC in cells and disrupts MYC–MAX interaction. MY05 engages intracellular c-MYC, modulates c-MYC thermal stability, reduces c-MYC transcriptional targets, and inhibits proliferation in cancer cells and tumor growth in mice. In summary, we identified a novel compound that directly interacts with c-MYC to disrupt the transcriptional program.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"68 6","pages":"6233–6251 6233–6251"},"PeriodicalIF":6.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria-Eleni Kouridaki, Jonathan Gillespie, John Robinson, Tanya Mathie, Laura Bain, Duncan McArthur, Angus Morrison, Daniel B. Greenslade, Michail Papadourakis, Kasia Maj, Kate Cameron, Darryl Turner, Scott P. Webster, Martin A. Wear, Dahlia Doughty-Shenton, Alison N. Hulme and Julien Michel*,
{"title":"Optimization of Cyclophilin B-Targeted Tri-vector Inhibitors for Novel MASH Treatments","authors":"Maria-Eleni Kouridaki, Jonathan Gillespie, John Robinson, Tanya Mathie, Laura Bain, Duncan McArthur, Angus Morrison, Daniel B. Greenslade, Michail Papadourakis, Kasia Maj, Kate Cameron, Darryl Turner, Scott P. Webster, Martin A. Wear, Dahlia Doughty-Shenton, Alison N. Hulme and Julien Michel*, ","doi":"10.1021/acs.jmedchem.5c0030110.1021/acs.jmedchem.5c00301","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c00301https://doi.org/10.1021/acs.jmedchem.5c00301","url":null,"abstract":"<p >Cyclophilins have been implicated in the pathophysiology of metabolic dysfunction-associated steatohepatitis (MASH). Pharmacological inhibition of the cyclophilin B isoform has the potential to attenuate liver fibrosis in MASH, but current cyclophilin inhibitors in clinical trials lack isoform selectivity. We previously reported the novel tri-vector small-molecule inhibitor <b>1</b> that exhibited improved subtype selectivity by simultaneously engaging three pockets on the surface of cyclophilins. Here, we present structure–activity relationships that address genotoxicity concerns, enhance subtype selectivity, improve pharmaceutical properties, and demonstrate strong efficacy in a MASH cellular model. Lead compound <b>11</b> is a potent cyclophilin B inhibitor with an encouraging pharmacokinetic profile suitable for further development.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"68 6","pages":"6815–6831 6815–6831"},"PeriodicalIF":6.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jmedchem.5c00301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeffrey S. Stehouwer*, Guofeng Huang, Dinahlee Saturnino Guarino, Manik L. Debnath, Ashok Polu, Steven J. Geib, Brian Lopresti, Milos D. Ikonomovic, Neale Mason, Robert H. Mach and Chester A. Mathis,
{"title":"Structure–Activity Relationships and Evaluation of 2-(Heteroaryl-cycloalkyl)-1H-indoles as Tauopathy Positron Emission Tomography Radiotracers","authors":"Jeffrey S. Stehouwer*, Guofeng Huang, Dinahlee Saturnino Guarino, Manik L. Debnath, Ashok Polu, Steven J. Geib, Brian Lopresti, Milos D. Ikonomovic, Neale Mason, Robert H. Mach and Chester A. Mathis, ","doi":"10.1021/acs.jmedchem.4c0298810.1021/acs.jmedchem.4c02988","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c02988https://doi.org/10.1021/acs.jmedchem.4c02988","url":null,"abstract":"<p >Structure–activity relationship studies were performed on a library of synthesized compounds based on previously identified tau ligands. The top 13 new compounds had <i>K</i><sub>i</sub> values in the range of 5–14 nM in Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) post-mortem brain tissues. One of the more promising new compounds ([<sup>3</sup>H]<b>75</b>) bound with high affinity in AD, PSP, and CBD tissues (<i>K</i><sub>D</sub>’s = 1–1.5 nM) and Pick’s disease tissue (<i>K</i><sub>D</sub> = 3.8 nM). Autoradiography studies with [<sup>3</sup>H]<b>75</b> demonstrated specific binding in AD, PSP, and CBD post-mortem tissues. Nonhuman primate brain PET imaging with [<sup>18</sup>F]<b>75</b> demonstrated a peak standardized uptake value (SUV) of ∼5 in the cerebellum, ∼4.5 in the cortex, and ∼4 in whole brain with SUV 2-to-90 min ratios of 3.9 in whole brain, 4.9 in cortex, and 4.5 in cerebellum. Compound [<sup>18</sup>F]<b>75</b> is a promising candidate for translation to human brain PET imaging studies.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"68 6","pages":"6462–6492 6462–6492"},"PeriodicalIF":6.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jmedchem.4c02988","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pierre Llompart, Kwame Amaning, Marc Bianciotto, Bruno Filoche-Rommé, Yann Foricher, Pablo Mas, David Papin, Jean-Philippe Rameau, Laurent Schio, Gilles Marcou, Alexandre Varnek, Mehdi Moussaid, Claire Minoletti, Paraskevi Gkeka
{"title":"Harnessing Medicinal Chemical Intuition from Collective Intelligence","authors":"Pierre Llompart, Kwame Amaning, Marc Bianciotto, Bruno Filoche-Rommé, Yann Foricher, Pablo Mas, David Papin, Jean-Philippe Rameau, Laurent Schio, Gilles Marcou, Alexandre Varnek, Mehdi Moussaid, Claire Minoletti, Paraskevi Gkeka","doi":"10.1021/acs.jmedchem.4c03066","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c03066","url":null,"abstract":"Over the past decade, collective intelligence, i.e., the intelligence that emerges from collective efforts, has transformed complex problem-solving and decision-making. In drug discovery, decision-making often relies on medicinal chemistry intuition. The present study explores the application of collective intelligence in drug discovery, focusing on lead optimization. Ninety-two Sanofi researchers with diverse expertise participated anonymously in an exercise centered on ADMET-related questions. Their feedback was used to build a collective intelligence agent, which was compared to an artificial intelligence model. The study led to three major conclusions: first, collective intelligence improves decision-making in optimizing ADMET endpoints, compared to individual decisions. Second, collective intelligence outperforms artificial intelligence for all other endpoints but hERG inhibition. Finally, we observe complementarity between collective human and artificial intelligence. Overall, this research highlights the potential of collective intelligence in drug discovery and the importance of a synergistic approach combining human and artificial intelligence in project decision making.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"54 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deyu Kong, Xiangbo Yang, Samantha Judd, Dan Yan, Stephanie Springborn, Michael A. Stashko, Adam Kidwell, Justus M. Huelse, Dmitri Kireev, Douglas K. Graham, Deborah DeRyckere, Brian Branchford, Xiaodong Wang
{"title":"UNC9426, a Potent and Orally Bioavailable TYRO3-Specific Inhibitor","authors":"Deyu Kong, Xiangbo Yang, Samantha Judd, Dan Yan, Stephanie Springborn, Michael A. Stashko, Adam Kidwell, Justus M. Huelse, Dmitri Kireev, Douglas K. Graham, Deborah DeRyckere, Brian Branchford, Xiaodong Wang","doi":"10.1021/acs.jmedchem.5c00048","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c00048","url":null,"abstract":"TYRO3 plays a critical role in platelet aggregation as a platelet response amplifier. Selective inhibition of TYRO3 may provide therapeutic benefits for treating thrombosis and related diseases without increasing bleeding risk. We employed a structure-based approach and discovered a novel and potent TYRO3 inhibitor UNC9426 (<b>12</b>) with an excellent Ambit selectivity score (<i>S</i><sub>50</sub> (1.0 μM) = 0.026) and favorable pharmacokinetic properties in mice. Treatment with UNC9426 reduced platelet aggregation without increasing bleeding time and blocked TYRO3-dependent functions in tumor cells and macrophages, implicating its utility for multiple indications.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"50 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeffrey S. Stehouwer, Guofeng Huang, Dinahlee Saturnino Guarino, Manik L. Debnath, Ashok Polu, Steven J. Geib, Brian Lopresti, Milos D. Ikonomovic, Neale Mason, Robert H. Mach, Chester A. Mathis
{"title":"Structure–Activity Relationships and Evaluation of 2-(Heteroaryl-cycloalkyl)-1H-indoles as Tauopathy Positron Emission Tomography Radiotracers","authors":"Jeffrey S. Stehouwer, Guofeng Huang, Dinahlee Saturnino Guarino, Manik L. Debnath, Ashok Polu, Steven J. Geib, Brian Lopresti, Milos D. Ikonomovic, Neale Mason, Robert H. Mach, Chester A. Mathis","doi":"10.1021/acs.jmedchem.4c02988","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c02988","url":null,"abstract":"Structure–activity relationship studies were performed on a library of synthesized compounds based on previously identified tau ligands. The top 13 new compounds had <i>K</i><sub>i</sub> values in the range of 5–14 nM in Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) post-mortem brain tissues. One of the more promising new compounds ([<sup>3</sup>H]<b>75</b>) bound with high affinity in AD, PSP, and CBD tissues (<i>K</i><sub>D</sub>’s = 1–1.5 nM) and Pick’s disease tissue (<i>K</i><sub>D</sub> = 3.8 nM). Autoradiography studies with [<sup>3</sup>H]<b>75</b> demonstrated specific binding in AD, PSP, and CBD post-mortem tissues. Nonhuman primate brain PET imaging with [<sup>18</sup>F]<b>75</b> demonstrated a peak standardized uptake value (SUV) of ∼5 in the cerebellum, ∼4.5 in the cortex, and ∼4 in whole brain with SUV 2-to-90 min ratios of 3.9 in whole brain, 4.9 in cortex, and 4.5 in cerebellum. Compound [<sup>18</sup>F]<b>75</b> is a promising candidate for translation to human brain PET imaging studies.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"19 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deyu Kong, Xiangbo Yang, Samantha Judd, Dan Yan, Stephanie Springborn, Michael A. Stashko, Adam Kidwell, Justus M. Huelse, Dmitri Kireev, Douglas K. Graham, Deborah DeRyckere*, Brian Branchford* and Xiaodong Wang*,
{"title":"UNC9426, a Potent and Orally Bioavailable TYRO3-Specific Inhibitor","authors":"Deyu Kong, Xiangbo Yang, Samantha Judd, Dan Yan, Stephanie Springborn, Michael A. Stashko, Adam Kidwell, Justus M. Huelse, Dmitri Kireev, Douglas K. Graham, Deborah DeRyckere*, Brian Branchford* and Xiaodong Wang*, ","doi":"10.1021/acs.jmedchem.5c0004810.1021/acs.jmedchem.5c00048","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c00048https://doi.org/10.1021/acs.jmedchem.5c00048","url":null,"abstract":"<p >TYRO3 plays a critical role in platelet aggregation as a platelet response amplifier. Selective inhibition of TYRO3 may provide therapeutic benefits for treating thrombosis and related diseases without increasing bleeding risk. We employed a structure-based approach and discovered a novel and potent TYRO3 inhibitor UNC9426 (<b>12</b>) with an excellent Ambit selectivity score (<i>S</i><sub>50</sub> (1.0 μM) = 0.026) and favorable pharmacokinetic properties in mice. Treatment with UNC9426 reduced platelet aggregation without increasing bleeding time and blocked TYRO3-dependent functions in tumor cells and macrophages, implicating its utility for multiple indications.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"68 6","pages":"6665–6682 6665–6682"},"PeriodicalIF":6.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structure-Based Optimization of Moracin M as Potent and Selective PDE4 Inhibitors with Antipsoriasis Effects","authors":"Furong Zhang, Tiansheng Zheng, Xue Wang, Yu Chen, Feng Zhang, Xingfu Liu, Sen Wang, Guofeng Yang, Shenghong Xie, Qi Wu, Chao Xu, Qian Zhou, Deyan Wu, Hai-Bin Luo, Yi-You Huang","doi":"10.1021/acs.jmedchem.5c00266","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c00266","url":null,"abstract":"Psoriasis is a complex chronic inflammatory disease that severely affects the quality of life of patients. However, current medications could only control the symptoms but not cure psoriasis with unmet medical needs. Herein, structure-based optimizations of natural product moracin M (IC<sub>50</sub> of 2.9 μM) led to a novel PDE4 inhibitor <b>L30</b> with greatly improved potency (IC<sub>50</sub> of 8.6 nM) and remarkable selectivity across other PDEs families (>201-fold). The binding pattern of <b>L30</b> with PDE4 revealed by cocrystal structure was different from that of roflumilast. Besides, <b>L30</b> could effectively inhibit the release of inflammatory cytokines and chemokines in Raw264.7 and HaCaT cell lines. Furthermore, topical administration of <b>L30</b> exhibited significant therapeutic effects in an imiquimod-induced psoriasis mouse model. These findings highlighted the potential of PDE4 inhibitor <b>L30</b> as a novel lead for the treatment of psoriasis.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"54 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structure-Based Optimization of Moracin M as Potent and Selective PDE4 Inhibitors with Antipsoriasis Effects","authors":"Furong Zhang, Tiansheng Zheng, Xue Wang, Yu Chen, Feng Zhang, Xingfu Liu, Sen Wang, Guofeng Yang, Shenghong Xie, Qi Wu, Chao Xu, Qian Zhou, Deyan Wu*, Hai-Bin Luo* and Yi-You Huang*, ","doi":"10.1021/acs.jmedchem.5c0026610.1021/acs.jmedchem.5c00266","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c00266https://doi.org/10.1021/acs.jmedchem.5c00266","url":null,"abstract":"<p >Psoriasis is a complex chronic inflammatory disease that severely affects the quality of life of patients. However, current medications could only control the symptoms but not cure psoriasis with unmet medical needs. Herein, structure-based optimizations of natural product moracin M (IC<sub>50</sub> of 2.9 μM) led to a novel PDE4 inhibitor <b>L30</b> with greatly improved potency (IC<sub>50</sub> of 8.6 nM) and remarkable selectivity across other PDEs families (>201-fold). The binding pattern of <b>L30</b> with PDE4 revealed by cocrystal structure was different from that of roflumilast. Besides, <b>L30</b> could effectively inhibit the release of inflammatory cytokines and chemokines in Raw264.7 and HaCaT cell lines. Furthermore, topical administration of <b>L30</b> exhibited significant therapeutic effects in an imiquimod-induced psoriasis mouse model. These findings highlighted the potential of PDE4 inhibitor <b>L30</b> as a novel lead for the treatment of psoriasis.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"68 6","pages":"6789–6803 6789–6803"},"PeriodicalIF":6.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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