ChemMedChem最新文献_第3页

Bilingua-DPP-IV: A Bimodal Fusion Convolutional Neural Network Model for Prediction of Dipeptidyl Peptidase IV Inhibitory Peptides Bilingua-DPP-IV：预测二肽基肽酶IV抑制肽的双峰融合卷积神经网络模型。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-10-23 DOI: 10.1002/cmdc.70551

Zhixing Zhang, Qiule Yu, Chen Yang, Hao Duan, Jiaojiao Fang, Jiahao Xu, Changda Gong, Weihua Li, Guixia Liu, Yun Tang

{"title":"Bilingua-DPP-IV: A Bimodal Fusion Convolutional Neural Network Model for Prediction of Dipeptidyl Peptidase IV Inhibitory Peptides","authors":"Zhixing Zhang, Qiule Yu, Chen Yang, Hao Duan, Jiaojiao Fang, Jiahao Xu, Changda Gong, Weihua Li, Guixia Liu, Yun Tang","doi":"10.1002/cmdc.70551","DOIUrl":"10.1002/cmdc.70551","url":null,"abstract":"Motivation: Dipeptidyl peptidase IV (DPP-IV) is a key therapeutic target for type 2 diabetes, and its inhibitory peptides are a promising class of therapeutic agents. However, the discovery of these promising drugs has been restricted, as many existing computational predictors are based on datasets that have remained static for several years.Results: Here, we first presented a newly curated and expanded benchmark dataset, then introduced Bilingua-DPP-IV, a bimodal deep learning framework that integrates features from both amino acid sequences and molecular structures. Our approach leveraged embeddings from the large-scale pretrained models ESM C and Uni-Mol2, processed through a convolutional neural network with an optimized gated fusion mechanism. On an independent test set, the Bilingua-DPP-IV ensemble model achieved a Matthews correlation coefficient of 0.764 and an area under the receiver operating characteristic curve of 0.963. On an external validation set, the model also demonstrated an accuracy of 0.898, exceeding the performance of existing state-of-the-art predictors, such as StructuralDPPIV.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 20","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242310","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

Anticancer Effect of Co(III) Complex of a Thiourea Derivative on Inhibiting Breast Cancer Cell Proliferation Using In Silico and In Vitro Evaluations 硫脲衍生物Co（III）配合物抑制乳腺癌细胞增殖的实验研究

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-10-22 DOI: 10.1002/cmdc.70544

Fatemeh Khodabakhshi, Somayeh Reiisi, Sajjad Rakhshani, Mehran Feizi-Dehnayebi

{"title":"Anticancer Effect of Co(III) Complex of a Thiourea Derivative on Inhibiting Breast Cancer Cell Proliferation Using In Silico and In Vitro Evaluations","authors":"Fatemeh Khodabakhshi, Somayeh Reiisi, Sajjad Rakhshani, Mehran Feizi-Dehnayebi","doi":"10.1002/cmdc.70544","DOIUrl":"https://doi.org/10.1002/cmdc.70544","url":null,"abstract":"Breast cancer remains a leading cause of cancer-related mortality worldwide, highlighting the need for novel therapeutic agents with improved selectivity and multifunctional activity. In this study, a novel cobalt(III) complex, Co(L2)3[L2 = 2-chloro-N-(2,2-dimethyloxazolidine-3-carbonothioyl)benzamide], was synthesized and evaluated using integrated in vitro and in silico approaches. The ligand and complex were characterized by FT-IR, UV–Vis, and 1H NMR spectroscopy. The antiproliferative activity was assessed in MCF-7, MDA-MB-231, and HUVEC cells using the MTT assay. IC50 values were 176.95 ± 2.84 µg/mL for MCF-7, 187.01 ± 0.47 µg/mL for MDA-MB-231, and 354.96 ± 1.14 µg/mL for HUVEC cells, corresponding to selectivity indices of 2.01 and 1.90, respectively. Co(L2)3 reduced colony formation and cell migration and increased glutathione reductase activity. Gene expression analysis showed upregulation of CASP3 and CASP9 and downregulation of BCL2, CDC25A, MMP2, and MMP9, indicating modulation of apoptosis-, cell-cycle-, and metastasis-related responses. Molecular docking predicted favorable interactions with CDC25A, MMP-2, and MMP-9. Collectively, these findings indicate that Co(L2)3 exhibits preferential in vitro anticancer activity against the tested breast cancer cell lines and warrant further investigation as a potential multifunctional anticancer agent.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 20","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258412","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

Gut-Derived α-Synuclein Condensates in Parkinson's Disease: Linking Liquid–Liquid Phase Separation, Blood Dissemination, and Chemical Biology 帕金森病中肠源性α-突触核蛋白凝聚物：连接液-液相分离、血液播散和化学生物学

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-10-22 DOI: 10.1002/cmdc.70545

Janci Arichandran, Shu-Huei Hsiao, Cheng-I Lee

{"title":"Gut-Derived α-Synuclein Condensates in Parkinson's Disease: Linking Liquid–Liquid Phase Separation, Blood Dissemination, and Chemical Biology","authors":"Janci Arichandran, Shu-Huei Hsiao, Cheng-I Lee","doi":"10.1002/cmdc.70545","DOIUrl":"https://doi.org/10.1002/cmdc.70545","url":null,"abstract":"Two advances have reshaped our understanding of α-synuclein (αSyn) in Parkinson's disease (PD). First, αSyn can assemble through liquid–liquid phase separation (LLPS) and related condensation pathways, forming condensates that mature into Lewy-body-like assemblies. Although conventional crowding-driven LLPS requires supraphysiological protein concentrations, membrane-templated surface condensation has been reported in vitro at ~10 nM, making this pathway plausible in the lipid-rich, electrically active enteric nervous system (ENS). Second, seeding-competent αSyn is detectable in blood before motor onset using seed-amplification assays. This review asks whether condensate-derived αSyn generated in the gut constitutes a blood-borne seed population that is systematically underrepresented by fibril-biased assays. We evaluate each step of the proposed pathway, including gut-specific LLPS triggers, release into and survival within the circulation, blood–brain barrier (BBB) traversal, and clinical detection, while distinguishing established evidence from indirect inference and testable hypotheses. Many of these questions are now experimentally accessible. Molecular rotors detect condensates through microviscosity rather than cross-β structure, condensate-stage modulators have emerged, and receptor-interception strategies such as bemcentinib provide opportunities for mechanistic interrogation. Together, these advances position chemical biology to determine whether condensate-derived seeds contribute to PD pathogenesis.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 20","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258432","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

Synthesis, Characterization, and In Vitro Evaluation of New Amino-Alcohol Quinolines as Promising Antimycobacterial Agents 新型氨基醇喹啉类抗菌药物的合成、表征及体外评价

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-10-22 DOI: 10.1002/cmdc.70543

Elise Si Ahmed Charrier, François Peltier, Jean-François Raimbert, Marie Perret, Claire Andréjak, Alexandra Dassonville-Klimpt, Pascal Sonnet

{"title":"Synthesis, Characterization, and In Vitro Evaluation of New Amino-Alcohol Quinolines as Promising Antimycobacterial Agents","authors":"Elise Si Ahmed Charrier, François Peltier, Jean-François Raimbert, Marie Perret, Claire Andréjak, Alexandra Dassonville-Klimpt, Pascal Sonnet","doi":"10.1002/cmdc.70543","DOIUrl":"10.1002/cmdc.70543","url":null,"abstract":"Nontuberculous mycobacteria (NTM) mainly Mycobacterium avium complex (MAC), are emerging pathogens responsible for pulmonary infections. Therefore, the effectiveness of the gold standard treatment is compromised by the emergence of intrinsic and acquired resistance of MAC. In this context, seventeen amino-alcohol quinolines as mefloquine analogs were developed as part of this work. Studies on the physicochemical properties, cytotoxicity and activity of these quinoline-based compounds, in relation to their structures, highlighted the important role of the trifluoromethyl and piperazine moieties. Thus, (R)-4c was identified as the most promising anti-MAC compound with the highest selectivity index value of 5.8. It was tested, in two-drug combinations, using a checkerboard assays with the standard antibiotics (clarithromycin, rifampicin and ethambutol), demonstrating an additive effect with each antibiotic of this gold standard treatment. These results confirm the potential of amino-alcohol quinolines as alternative of current anti-NTM agents.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 20","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149259900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A KATing Edge Perspective on KAT6A Inhibitors as Anticancer Agents KAT6A抑制剂抗癌研究进展

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-10-22 DOI: 10.1002/cmdc.70534

Rochelle Woodland, Adi Suwandi, Awgichew Behaile Teklemariam, Nidhish Francis, Li Li, Kenneth A. Chinkwo, Jonathan B. Baell, David J. Leaver

引用次数: 0

Liposomal Formulation of Ellagic Acid Counteracts Amyloid-β Oligomer-Induced Cellular Stress: Influence of Neuronal Differentiation 脂质体配方鞣花酸抵消淀粉样蛋白-β寡聚物诱导的细胞应激：神经元分化的影响

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-10-22 DOI: 10.1002/cmdc.70546

Rebecca Castellacci, Federica Carnemolla, Manuela Leri, Monica Bucciantini, Maria Camilla Bergonzi

{"title":"Liposomal Formulation of Ellagic Acid Counteracts Amyloid-β Oligomer-Induced Cellular Stress: Influence of Neuronal Differentiation","authors":"Rebecca Castellacci, Federica Carnemolla, Manuela Leri, Monica Bucciantini, Maria Camilla Bergonzi","doi":"10.1002/cmdc.70546","DOIUrl":"https://doi.org/10.1002/cmdc.70546","url":null,"abstract":"Ellagic acid (EA) is a polyphenolic compound with antioxidant and neuroprotective properties whose therapeutic application is limited by poor aqueous solubility, low permeability and limited stability. In this study, EA-loaded liposomes (F2) were developed and characterized to improve its biopharmaceutical properties and evaluate its protective effects against amyloid-β (Aβ) oligomer-induced cellular stress. F2 showed favorable physicochemical characteristics, storage stability, and stability in the presence of human serum albumin, while providing sustained EA release. In the BBB-PAMPA assay, F2 maintained measurable passive EA permeability while allowing higher EA amount permeated. The biological effects of EA and F2 were subsequently evaluated in undifferentiated and retinoic acid-differentiated SH-SY5Y cells (RA-SH-SY5Y) exposed to Aβ oligomers. In undifferentiated cells, F2 showed a distinct concentration-dependent protective profile, particularly at 10 μM, associated with preservation of cellular metabolic activity, attenuation of ROS accumulation and partial preservation of mitochondrial-associated functional and morphological parameters. In RA-SH-SY5Y, EA and F2 showed broadly comparable protective effects. Overall, liposomes improved the biopharmaceutical properties of EA while preserving or enhancing its biological activity against Aβ-induced cellular stress. The differential responses observed in undifferentiated and RA-SH-SY5Y cells further suggest that the biological advantage associated with liposomal formulation may be influenced by cellular phenotype.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 20","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258433","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

Riluzole-Derived Benzo[d]thiazoles as CK1δ Inhibitors for Amyotrophic Lateral Sclerosis-Related Neurodegeneration 利鲁唑类苯并噻唑作为肌萎缩侧索硬化症相关神经变性的CK1δ抑制剂

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-10-22 DOI: 10.1002/cmdc.70539

Simone Adorinni, Ilenia Grieco, Stefano Morasso, Michelle Fornasier, Gianluca Novello, Veronica Salmaso, Loreto Martínez-González, Eleonora Cescon, Davide Bassani, Giovanni Adriano Bassan, Teresa Gianferrara, Filippo Prencipe, Veronika Kost, Tatiana Da Ros, Paola Storici, Ana Martinez, Giampiero Spalluto, Stefano Moro, Stephanie Federico

{"title":"Riluzole-Derived Benzo[d]thiazoles as CK1δ Inhibitors for Amyotrophic Lateral Sclerosis-Related Neurodegeneration","authors":"Simone Adorinni, Ilenia Grieco, Stefano Morasso, Michelle Fornasier, Gianluca Novello, Veronica Salmaso, Loreto Martínez-González, Eleonora Cescon, Davide Bassani, Giovanni Adriano Bassan, Teresa Gianferrara, Filippo Prencipe, Veronika Kost, Tatiana Da Ros, Paola Storici, Ana Martinez, Giampiero Spalluto, Stefano Moro, Stephanie Federico","doi":"10.1002/cmdc.70539","DOIUrl":"https://doi.org/10.1002/cmdc.70539","url":null,"abstract":"Riluzole-derived benzo[d]thiazoles were investigated as metabolite-inspired CK1δ inhibitors, a kinase involved in TDP-43 phosphorylation and therefore relevant to amyotrophic lateral sclerosis (ALS). Starting from the known CK1δ activity of riluzole, we examined whether its major hydroxylamine metabolite could preserve target recognition and provide a rational entry point for scaffold optimisation. The metabolite retained CK1δ inhibition, but its limited chemical stability and toxicity in neuronal cells identified the hydroxylamine group as a critical liability. Replacement of this functionality with a hydrazine converted the fragile metabolite-derived structure into a more potent and tractable CK1δ inhibitor series. Structure–activity relationship studies revealed that the hydrazine moiety accommodates broader substitution than the hydroxylamine counterparts, with branched alkyl and benzyl groups giving the most balanced profiles. Docking and molecular dynamics suggested that the improvement could be attributed to an additional hydrogen-bond with Gly86 in the hinge region. The best derivative combined submicromolar CK1δ inhibition with passive blood–brain barrier permeability, short-term cellular tolerance, ATP competitive inhibition, direct target engagement, and preliminary selectivity over GSK3β. Although this compound did not result neuroprotective in an oxidative stress model, it paves the way for a focused benzo[d]thiazole platform for probing CK1δ biology in ALS.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 20","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.70539","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

On Organic-Molecule and Peptide Non-Covalent Inhibitors of the TP53-MDM2/MDMX Interaction: An Inside View From the Interaction Energy at Residue-to-Residue Level TP53-MDM2/MDMX相互作用的有机-分子和肽非共价抑制剂：从残基-残基水平相互作用能的内部视角

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-10-21 DOI: 10.1002/cmdc.70477

Francesco Pietra

{"title":"On Organic-Molecule and Peptide Non-Covalent Inhibitors of the TP53-MDM2/MDMX Interaction: An Inside View From the Interaction Energy at Residue-to-Residue Level","authors":"Francesco Pietra","doi":"10.1002/cmdc.70477","DOIUrl":"10.1002/cmdc.70477","url":null,"abstract":"Depletion of the tumor-suppressor TP53 is known to open the door to cancer and, after 30 years of research, no remedy has been approved. When TP53 depletion is due to trapping by MDM2, a key requisite for non-covalent inhibitors is high affinity for MDM2 (and also for the MDMX analog, which plays an indirect role in depleting TP53). While inhibitor performance has always been measured by the binding energy, the present work offers a deeper view by evaluating the interaction energy and its electrostatic and vdW components at residue-to-residue level. In the absence of suitable experimental methods, the task was addressed using unrestricted MD and QM-MM, including all inhibitors that are currently in clinical trials, and for which the static structure at high resolution has been made available. It has emerged, in the framework of weak, dispersion-driven interactions that rarely exceed 6 kcal/mol, and with water solvation playing a major role, where the inhibitors bind better and where repulsions arise. In this scenario, a better pattern of interaction energies emerged with stabilized peptides than with organic-molecule inhibitors. All that should help designing the next generation of inhibitors.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 20","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236251","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

Validation of Small-Molecule Entry Inhibitors Targeting the Respiratory Syncytial Virus 针对呼吸道合胞病毒的小分子进入抑制剂的验证。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-10-21 DOI: 10.1002/cmdc.70501

Christina Karhan, Svenja M. Sake, Melanie Urbanek-Quaing, Diletta Bergamo, Jessica Rückert, Jiabin Huang, Christina Grethe, Antonia P. Gunesch, Anne Kühnel, Birthe Reinecke, Nicole Fischer, Thomas F. Schulz, Thomas Pietschmann, Anna K. H. Hirsch

{"title":"Validation of Small-Molecule Entry Inhibitors Targeting the Respiratory Syncytial Virus","authors":"Christina Karhan, Svenja M. Sake, Melanie Urbanek-Quaing, Diletta Bergamo, Jessica Rückert, Jiabin Huang, Christina Grethe, Antonia P. Gunesch, Anne Kühnel, Birthe Reinecke, Nicole Fischer, Thomas F. Schulz, Thomas Pietschmann, Anna K. H. Hirsch","doi":"10.1002/cmdc.70501","DOIUrl":"10.1002/cmdc.70501","url":null,"abstract":"Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections worldwide, particularly in infants, young children, and elderly individuals. Despite the availability of preventive options such as vaccines and monoclonal antibodies, effective antiviral therapies for acute infections remain limited. Therefore, we investigated small-molecule entry inhibitors identified in a high-throughput campaing and evaluated the most promising candidates in detail by performing resynthesis and determining their antiviral activity. Unfortunately, analytical investigations by nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry (LC–MS) revealed discrepancies between the screening samples and the resynthesized compounds for two compound classes, highlighting the complexity of hit validation and the potential influence of impurities. By publishing these results, we aim not only to underscore the importance of rigorous analytical and biological validation in screening campaigns but also to support the development of improved strategies for identifying reliable RSV inhibitors. We also believe it is important to publish false-positive hits to avoid time efforts on projects that assume such compounds as genuine hits.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 20","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic and Biomedical Applications of Dopamine-Derived Scaffolds: A Comprehensive Review 多巴胺衍生支架的治疗和生物医学应用综述

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-10-19 DOI: 10.1002/cmdc.70547

Babak Kaboudin, Atefe Barati

引用次数: 0