ChemMedChem最新文献

AZP2006 (Ezeprogind^®): a Promising New Drug Candidate in the Battle Against Neurodegenerative Diseases.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-27 DOI: 10.1002/cmdc.202400891

Philippe Verwaerde, Olivier Defert

{"title":"AZP2006 (Ezeprogind®): a Promising New Drug Candidate in the Battle Against Neurodegenerative Diseases.","authors":"Philippe Verwaerde, Olivier Defert","doi":"10.1002/cmdc.202400891","DOIUrl":"https://doi.org/10.1002/cmdc.202400891","url":null,"abstract":"Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder characterized by abnormal tau protein accumulation. This perspective article explores AZP2006 (INN: Ezeprogind), a novel small molecule targeting the Progranulin (PGRN) and Prosaposin (PSAP) axis to enhance lysosomal health in PSP treatment. AZP2006 stabilizes the PGRN-PSAP complex, improving lysosomal function and reducing tau pathology. Preclinical studies in tauopathy models demonstrated AZP2006's ability to decrease tau hyperphosphorylation, enhance neuronal survival, mitigate neuroinflammation and promote synaptogenesis. Clinical trials have shown AZP2006 to be well-tolerated in healthy volunteers and PSP patients. A Phase 2a study met its primary endpoints, as it provided valuable safety data and even encouraged further investigation of its efficacy in a larger clinical study. An upcoming Phase 2b/3 trial aims to assess long-term safety and efficacy in a larger PSP cohort. AZP2006's mechanism of action strongly suggests potential applications in other tauopathies, including Alzheimer's and Parkinson's diseases. By addressing lysosomal dysfunction and tau pathology, AZP2006 represents a promising disease-modifying approach for PSP and other neurodegenerative disorders.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400891"},"PeriodicalIF":3.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Benzamide derivatives of thioacridine as DYRK2 and DYRK3 dual inhibitors.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-27 DOI: 10.1002/cmdc.202500122

Jean Roussel, Shreya Kashyap, Sourav Banerjee, Thierry Lomberget, François Hallé

{"title":"Benzamide derivatives of thioacridine as DYRK2 and DYRK3 dual inhibitors.","authors":"Jean Roussel, Shreya Kashyap, Sourav Banerjee, Thierry Lomberget, François Hallé","doi":"10.1002/cmdc.202500122","DOIUrl":"https://doi.org/10.1002/cmdc.202500122","url":null,"abstract":"DYRK2 has become a promising therapeutic target due to its involvement in various processes, including regulation of protein stability and phosphorylation events related to neurodegenerative diseases and cancers. The thioacridine derivative LDN-192960 has been widely recognized as a potent inhibitor of DYRK2. However, it also inhibits other kinases, such as DYRK3, Haspin, DYRK1A and CLK1, making it challenging to delineate the biological roles of DYRK2. In this study, we designed and synthesized a series of benzamide derivatives of the thioacridine LDN-192960, to improve selectivity and potency towards DYRK2. Several compounds demonstrated potent inhibition of DYRK2 and DYRK3, with IC50 values in the nanomolar range. Notably, the para-substituted aldehyde derivative 10f exhibited significant selectivity for DYRK2/DYRK3 against its main off-targets DYRK1A, CLK1 and Haspin, thus surpassing the selectivity profile of LDN-192960. Docking studies revealed new interactions between 10f and DYRK2, compared to LDN-192960 / DYRK2 co-crystallized structure and 10f was shown to impair proteasome activity in HEK293 cells. These findings highlight the pharmacophore study of DYRK2/DYRK3 dual inhibitors, and present compound 10f as a selective chemical probe for DYRK2 and DYRK3, that might be an essential tool for elucidating the specific biological roles of these kinases and advancing targeted therapeutic applications.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500122"},"PeriodicalIF":3.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Ligand Screening and Discovery using Cocktail Soaking and Automated MicroED.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-26 DOI: 10.1002/cmdc.202500156

Jieye Lin, Marc J Gallenito, Johan Hattne, Tamir Gonen

引用次数: 0

Exploiting the 5-amino-11H-indolo[3,2-c]isoquinoline Core to Achieve Better G-quadruplex Ligands for Cancer Therapy.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-26 DOI: 10.1002/cmdc.202401019

Israa M Aljnadi, Barbara Bahls, Noélia Duarte, Bruno L Victor, Eduarda Mendes, Sergio P Camões, Joana P Miranda, Ermelinda Maçôas, Alexandra Paulo

{"title":"Exploiting the 5-amino-11H-indolo[3,2-c]isoquinoline Core to Achieve Better G-quadruplex Ligands for Cancer Therapy.","authors":"Israa M Aljnadi, Barbara Bahls, Noélia Duarte, Bruno L Victor, Eduarda Mendes, Sergio P Camões, Joana P Miranda, Ermelinda Maçôas, Alexandra Paulo","doi":"10.1002/cmdc.202401019","DOIUrl":"https://doi.org/10.1002/cmdc.202401019","url":null,"abstract":"G-quadruplexes (G4) are secondary structures that can form within guanine-rich nucleic acids and have cell proliferation regulatory functions. Targeting DNA G4 structures has emerged as a promising anticancer therapy, highlighting the need for new G4 ligands with reduced number of cationic groups to ensure lower toxicity. In this study, we report the synthesis of mono- and di-substituted 5-amino-11H-indolo[3,2-c]isoquinolines. Fluorescence spectroscopy studies indicate that substitution in position 11 dictates the preference of binding to different G4. Compound 10, which features a ethylpyrrolidine side chain, demonstrated a binding preference by one order of magnitude for parallel c-MYCG4 (Kb = 107 M-1), over parallel k-RASG4 (Kb = 106 M-1), hybrid TeloG4 and dsDNA (Kb = 105 M-1). Molecular docking studies revealed that compound 10 can bind not only to the flat G-quartets but also to bridge between two loops of c-MYCG4 through hydrogen bonds, which may explain its capacity to discriminate between G4. Moreover, compound 10 drastically reduced the cell viability of breast cancer cells at a concentration of 10 µM. Overall, herein we report the discovery of a new potent and selective G4 ligand, with reduced number of side chains and antiproliferative activity in cancer cells that deserves to be further investigated.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202401019"},"PeriodicalIF":3.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Carborane-based Analogues of Celecoxib and Flurbiprofen, their COX Inhibition Potential and COX Selectivity Index.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-24 DOI: 10.1002/cmdc.202500166

Lea Ueberham, Jonas Schädlich, Kim Schramke, Sebastian Braun, Christoph Selg, Markus Laube, Peter Lönnecke, Jens Pietzsch, Evamarie Hey-Hawkins

{"title":"Carborane-based Analogues of Celecoxib and Flurbiprofen, their COX Inhibition Potential and COX Selectivity Index.","authors":"Lea Ueberham, Jonas Schädlich, Kim Schramke, Sebastian Braun, Christoph Selg, Markus Laube, Peter Lönnecke, Jens Pietzsch, Evamarie Hey-Hawkins","doi":"10.1002/cmdc.202500166","DOIUrl":"https://doi.org/10.1002/cmdc.202500166","url":null,"abstract":"The cylcooxygenase isoforms COX-1 and COX-2 are involved in the production of prostaglandins in physiological and pathological processes. The overexpression of COX-2 under inflammatory conditions as well as its role in cancer and neurodegenerative diseases necessitates the need to develop and improve non-steroidal anti-inflammatory drugs. These COX inhibitors are used to reduce the symptoms of inflammation, with aspirin, indomethacin or flurbiprofen being prominent examples. To reduce unwanted side effects connected with unselective inhibition, the development of novel COX-2 selective inhibitors is important. We herein describe the synthesis, characterization, and in vitro biological evaluation of eight flurbiprofen- and celecoxib-based carborane analogues. Carboranes as hydrophobic surrogates are suitable substituents that can contribute to a selectivity increase towards COX-2, due to size-exclusion. The inhibitory efficacy for COX-1 and COX-2 of the four ortho- and four nido-carborane derivatives has been tested. The nido compounds are much more potent than their closo-carborane analogues. Celecoxib-based compound 10 showed an IC50 value in the sub-µM range for COX-2 and in contrast to its ortho-carborane derivative a reversed selectivity preference for COX-2 instead of COX-1. While none of these carborane derivatives outperformed their organic analogues, the flurbiprofen-based nido-carborane derivatives 14a and 14b surpassed the known carborane-based flurbiprofen analogues.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500166"},"PeriodicalIF":3.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Nicorandil repurposing in orofacial pain: preclinical findings in adult zebrafish.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-22 DOI: 10.1002/cmdc.202401007

José Ismael de Araújo, Gerlânia Leite, Leonardo da Silva-Neto, Antonio Eufrásio Vieira-Neto, Angelo de Fátima, Adriana Rolim Campos

{"title":"Nicorandil repurposing in orofacial pain: preclinical findings in adult zebrafish.","authors":"José Ismael de Araújo, Gerlânia Leite, Leonardo da Silva-Neto, Antonio Eufrásio Vieira-Neto, Angelo de Fátima, Adriana Rolim Campos","doi":"10.1002/cmdc.202401007","DOIUrl":"https://doi.org/10.1002/cmdc.202401007","url":null,"abstract":"This study investigated the orofacial antinociceptive activity of nicorandil in adult zebrafish and explored the involvement of TRP channels in this effect. Nicorandil, a known antianginal drug, reduced nociceptive behaviors induced by capsaicin (TRPV1 agonist), cinnamaldehyde (TRPA1 agonist), and menthol (TRPM8 agonist) without altering the locomotor activity of the zebrafish. Pre-treatment with specific TRPA1 and TRPV1 antagonists prevented the antinociceptive effects of nicorandil, indicating its action on these channels. Molecular docking studies supported these findings, demonstrating high chemical affinity and specific binding of nicorandil to the TRPV1 and TRPA1 channels, leading to stabilization and reduced biological activity of these channels. In contrast, the antinociceptive effect of nicorandil on menthol-induced nociception was not affected by a TRPM8 antagonist, suggesting that TRPM8 modulation is not involved in nicorandil's mechanism of action. The study highlights the potential of nicorandil as an analgesic through its interaction with TRPV1 and TRPA1 channels, providing a molecular basis for repositioning nicorandil as an effective analgesic drug.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202401007"},"PeriodicalIF":3.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Two Targets, One Mission: Heterobivalent Metal-based Radiopharmaceuticals for Prostate Cancer Imaging and Therapy.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-21 DOI: 10.1002/cmdc.202500128

António Paulo, Margarida Sobral, Sandra I Mota, Paulo J Oliveira, Ana M Urbano

{"title":"Two Targets, One Mission: Heterobivalent Metal-based Radiopharmaceuticals for Prostate Cancer Imaging and Therapy.","authors":"António Paulo, Margarida Sobral, Sandra I Mota, Paulo J Oliveira, Ana M Urbano","doi":"10.1002/cmdc.202500128","DOIUrl":"https://doi.org/10.1002/cmdc.202500128","url":null,"abstract":"Prostate cancer (PCa) is a significant healthcare challenge, associated with considerable mortality and morbidity among men, particularly in developed countries. PCa mortality and morbidity are primarily related to its most advanced form, metastatic castration-resistant PCa (mCRPC), for which there is presently no cure. Therefore, novel therapeutic approaches to increase mCRPC survival are critically needed. Due to PCa tumor heterogeneity and complex tumor microenvironment, the efficacy of single-target radiopharmaceuticals, such as the Food and Drug Administration (FDA)-approved 177Lu-PSMA-617, is currently under reassessment. The design and development of PCa dual-target radiopharmaceuticals have garnered considerable attention, due to their benefits over single-target counterparts, namely increased therapeutic specificity and efficacy, as well as the ability to overcome the challenge of inconsistent tumor visualization caused by variable receptor expression across diverse lesions, thereby enabling more comprehensive imaging. Several PCa biomarkers are currently being investigated as potential targets for dual-target radiopharmaceuticals, including prostate-specific membrane antigen (PSMA), gastrin-releasing peptide receptor (GRPR), integrin αvβ3 receptor, albumin, bisphosphonates, fibroblast activation protein (FAP), sigma-1 receptor, as well as, radiosensitive organelles like mitochondria and the nucleus. This review explores recent advancements in heterobivalent metal-based radiopharmaceuticals for dual targeting in PCa, highlighting their significance in theranostic and personalized medicine.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500128"},"PeriodicalIF":3.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Small-Molecule KRAS Inhibitors by Tyrosine Covalent Bond Formation.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-18 DOI: 10.1002/cmdc.202400624

Alexander Landgraf, Robert Brenner, Mona Ghozayel, Khuchtumur Bum-Erdene, Giovanni Gonzalez-Gutierrez, Samy Meroueh

{"title":"Small-Molecule KRAS Inhibitors by Tyrosine Covalent Bond Formation.","authors":"Alexander Landgraf, Robert Brenner, Mona Ghozayel, Khuchtumur Bum-Erdene, Giovanni Gonzalez-Gutierrez, Samy Meroueh","doi":"10.1002/cmdc.202400624","DOIUrl":"https://doi.org/10.1002/cmdc.202400624","url":null,"abstract":"The development of the KRAS G12C inhibitor sotorasib was a major advance towards drugging KRAS. However, the G12C mutation is only found in about 10% of tumors with a KRAS mutation. KRAS tyrosine amino acids could provide alternative sites for covalent drug development. Here, we screen a library of aryl sulfonyl fluorides to explore whether tyrosines on KRAS are accessible for covalent bond formation. We identify compound 1 (SOF-436), which inhibits KRAS nucleotide exchange by guanine exchange factor SOS1 and the binding of KRAS to effector protein RAF. Tyr-64 was the major reaction site of 1 (SOF-436), although minor reaction at Tyr-71 was also observed. The fragment engages the Switch II pocket of KRAS based on mass spectrometry, nucleotide exchange, effector protein binding, nuclear magnetic resonance (NMR), and molecular dynamics simulations. Co-crystal structures of smaller fragments covalently bound to KRAS at Tyr-71 provide a strategy for the development of Switch I/II KRAS covalent inhibitors. A NanoBRET assay revealed that the compound and its analogs inhibit KRAS binding to RAF in mammalian cells. Although not yet suitable as chemical probes, these fragments provide starting points for small molecules to investigate tyrosine as a nucleophile for covalent inhibition of KRAS in tumors.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400624"},"PeriodicalIF":3.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A novel inhibitor against the Bromodomain Protein 1 of the malaria pathogen Plasmodium falciparum.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-18 DOI: 10.1002/cmdc.202500024

Marius Amann, Robin Warstat, Kay Kristin Rechten, Philip Theuer, Magdalena Schustereder, Sophie Clavey, Bernhard Breit, Oliver Einsle, Martin Hügle, Michaela Petter, Stefan Günther

{"title":"A novel inhibitor against the Bromodomain Protein 1 of the malaria pathogen Plasmodium falciparum.","authors":"Marius Amann, Robin Warstat, Kay Kristin Rechten, Philip Theuer, Magdalena Schustereder, Sophie Clavey, Bernhard Breit, Oliver Einsle, Martin Hügle, Michaela Petter, Stefan Günther","doi":"10.1002/cmdc.202500024","DOIUrl":"https://doi.org/10.1002/cmdc.202500024","url":null,"abstract":"The rise of drug resistances in malaria necessitates the exploration of novel therapeutic strategies. Targeting epigenetic pathways could open new, promising treatment avenues. In this study, we focus on the essential Bromodomain Protein 1 (PfBDP1) of the malaria pathogen Plasmodium falciparum. Utilizing the pan-selective bromodomain inhibitor MPM6, we identified a potent initial hit and subsequently developed it into a nanomolar binder. Through a combination of virtual docking, isothermal titration calorimetry, and X-ray crystallography, we elucidated the molecular interactions of the new inhibitors with the bromodomain (BRD) of the protein (PfBDP1-BRD). Our findings include the first co-crystallized inhibitors with the structures of PfBRD1-BRD as well as the bromodomain of the close homologous protein of Plasmodium vivax (PvBDP1-BRD). The structures provide new insights into their binding mechanisms. Further validation using conditional knockdown of PfBDP1 in P. falciparum demonstrated parasite sensitivity to the inhibitor, underscoring its potential in a targeted therapeutic approach against malaria.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500024"},"PeriodicalIF":3.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Advances in Diclofenac Derivatives: Exploring Carborane-Substituted N-Methyl and Nitrile Analogs for Anti-Cancer Therapy.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-18 DOI: 10.1002/cmdc.202500084

Christoph Selg, Robert Schuster, Aleksandr Kazimir, Peter Lönnecke, Mara Wolniewicz, Jonas Schädlich, Markus Laube, Jens Pietzsch, Vuk Gordić, Tamara Krajnović, Sanja Mijatović, Danijela Maksimović-Ivanić, Evamarie Hey-Hawkins

{"title":"Advances in Diclofenac Derivatives: Exploring Carborane-Substituted N-Methyl and Nitrile Analogs for Anti-Cancer Therapy.","authors":"Christoph Selg, Robert Schuster, Aleksandr Kazimir, Peter Lönnecke, Mara Wolniewicz, Jonas Schädlich, Markus Laube, Jens Pietzsch, Vuk Gordić, Tamara Krajnović, Sanja Mijatović, Danijela Maksimović-Ivanić, Evamarie Hey-Hawkins","doi":"10.1002/cmdc.202500084","DOIUrl":"https://doi.org/10.1002/cmdc.202500084","url":null,"abstract":"This study explores the anti-cancer potential of N-methylated open-ring derivatives of carborane-substituted diclofenac analogs. By N-methylation, the open-chain form could be trapped and cyclization back to lactam or amidine derivatives was inhibited. A small library of carborane- and phenyl-based secondary and tertiary arylamines bearing carboxylic acid or nitrile groups was synthesized and analyzed for their COX-affinity in vitro and in silico. The compounds were further evaluated against mouse adenocarcinoma (MC38), human colorectal carcinoma (HCT116) and human colorectal adenocarcinoma (HT29) cell lines and showed potent cytotoxicity. Additional biological assessments of the mode of action were performed using flow cytometric techniques and fluorescence microscopy. The data obtained revealed a common antiproliferative effect coupled with the induction of caspase-independent apoptosis and the specific effects of the compound on the phenotype of MC38 cells, resulting in impaired cell viability of MC38 cells and satisfactory selectivity exceeding the antitumor activity of diclofenac.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500084"},"PeriodicalIF":3.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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