ChemMedChem最新文献_第9页

Front Cover: Rational Design of Novel Allosteric EYA2 Inhibitors as Potential Therapeutics for Multiple Brain Cancers (ChemMedChem 18/2024) 封面：作为多种脑癌潜在治疗药物的新型异位EYA2抑制剂的合理设计（ChemMedChem 18/2024）

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-16 DOI: 10.1002/cmdc.202481801

Lukas Gardner, John Rossi, Brock Armstrong, Mia Muse, Alex LaVeck, Melanie A. Blevins, Lingdi Zhang, Dr. Heide L. Ford, Dr. Rui Zhao, Dr. Xiang Wang

引用次数: 0

Discovery of ICOS-Targeted Small Molecules Using Affinity Selection Mass Spectrometry Screening 利用亲和选择质谱筛选发现 ICOS 靶向小分子化合物

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-13 DOI: 10.1002/cmdc.202400545

Longfei Zhang, Laura Calvo-Barreiro, Victor de Sousa Batista, Katarzyna Świderek, Moustafa T. Gabr

{"title":"Discovery of ICOS-Targeted Small Molecules Using Affinity Selection Mass Spectrometry Screening","authors":"Longfei Zhang, Laura Calvo-Barreiro, Victor de Sousa Batista, Katarzyna Świderek, Moustafa T. Gabr","doi":"10.1002/cmdc.202400545","DOIUrl":"10.1002/cmdc.202400545","url":null,"abstract":"Inducible T cell co-stimulator (ICOS) is a positive immune checkpoint receptor expressed on the surface of activated T cells, which could promote cell function after being stimulated with ICOS ligand (ICOS−L). Although clinical benefits have been reported in the ICOS modulation-based treatment for cancer and autoimmune disease, current modulators are restricted in biologics, whereas ICOS-targeted small molecules are lacking. To fill this gap, we performed an affinity selection mass spectrometry (ASMS) screening for ICOS binding using a library of 15,600 molecules. To the best of our knowledge, this is the first study that utilizes ASMS screening to discover small molecules targeting immune checkpoints. Compound 9 with a promising ICOS/ICOS−L inhibitory profile (IC50=29.38±3.41 μM) was selected as the template for the modification. Following preliminary structure-activity relationship (SAR) study and molecular dynamic (MD) simulation revealed the critical role of the ortho-hydroxy group on compound 9 in the ICOS binding, as it could stabilize the interaction via the hydrogen bond formation with residuals on the glycan, and the depletion could lead to an activity lost. This work validates a promising inhibitor for the ICOS/ICOS−L interaction, and we anticipate future modifications could provide more potent modulators for this interaction.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"19 22","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256297","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

Breaking Barriers in Photothermal Tumor Therapy: A Cascade of Strain-Engineered Nanozyme in Action 打破肿瘤光热疗法的障碍：一连串应变工程纳米酶在发挥作用

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-13 DOI: 10.1002/cmdc.202400443

Srinidhi V. G., Huidrom Mangalsana, Amit Vernekar

引用次数: 0

Biomimetic Cell Membrane-Coated Nanoparticles for Cancer Theranostics 用于癌症血清学的仿生细胞膜包覆纳米粒子

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-12 DOI: 10.1002/cmdc.202400410

Tiantian Jiang, Yiduo Zhan, Jiayao Ding, Zheming Song, Yijing Zhang, Jingchao Li, Ting Su

{"title":"Biomimetic Cell Membrane-Coated Nanoparticles for Cancer Theranostics","authors":"Tiantian Jiang, Yiduo Zhan, Jiayao Ding, Zheming Song, Yijing Zhang, Jingchao Li, Ting Su","doi":"10.1002/cmdc.202400410","DOIUrl":"10.1002/cmdc.202400410","url":null,"abstract":"Nanoparticles can enhance drugs accumulating at the tumor site and hold tremendous promise for achieving effective tumor treatment. However, due to the complexity of cancer heterogeneity and suppressive tumor microenvironment, the delivery of traditional nanoparticles has poor infiltration and off-target effects, making it difficult to control the drug release rate and causing off-target toxicity. In recent years, cell membrane-coated biomimetic nanoparticles have been developed, which have both the natural characteristics of biomembranes and the physical characteristics of traditional nanoparticles, thus improving the homologous targeting ability of nanoparticles to tumor cells and better biocompatibility. In this paper, we reviewed the application of single cell membrane and hybrid cell membrane-coated biomimetic nanoparticles in the integration for tumor diagnosis and treatment. We talked about the preparation methods of cell membrane-coated nanoparticles, the targeting mechanisms, and the effects of imaging and therapeutic outcomes of different cell membrane-coated biomimetic nanoparticles in detail. Finally, we discussed the existing problems and prospects of cell membrane-coated biomimetic nanomaterials.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"19 22","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201659","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

Flavonol‐ruthenium complexes as antioxidant and anticancer agents 作为抗氧化剂和抗癌剂的黄酮醇钌复合物

IF 3.4 4区医学

ChemMedChem Pub Date : 2024-09-12 DOI: 10.1002/cmdc.202400313

Tzenge-Lien Shih, Ting-Wei Wu, Yi-Cheng Chu, Chuan-Hsin Chang, Yu-Hui Hsieh, Mei-Hsin Tang, Pei-Hsuan Hsu, Jih-Jung Chen

引用次数: 0

Structural basis for inhibition of the SARS‐CoV‐2 nsp16 by substrate‐based dual site inhibitors 基于底物的双位点抑制剂抑制 SARS-CoV-2 nsp16 的结构基础

IF 3.4 4区医学

ChemMedChem Pub Date : 2024-09-11 DOI: 10.1002/cmdc.202400618

Gints Kalnins, Laura Rudusa, Anna Bula, Diana Zelencova-Gopejenko, Olga Bobileva, Mihails Sisovs, Kaspars Tars, Aigars Jirgensons, Kristaps Jaudzems, Raitis Bobrovs

引用次数: 0

Factors Affecting Liquid‐Liquid Phase Separation of RGG Peptides with DNA G‐Quadruplex 影响RGG肽与DNA G-四联体液-液相分离的因素

IF 3.4 4区医学

ChemMedChem Pub Date : 2024-09-11 DOI: 10.1002/cmdc.202400460

Daisuke Miyoshi, Sumit Shil, Mitsuki Tsuruta, Keiko Kawauchi

{"title":"Factors Affecting Liquid‐Liquid Phase Separation of RGG Peptides with DNA G‐Quadruplex","authors":"Daisuke Miyoshi, Sumit Shil, Mitsuki Tsuruta, Keiko Kawauchi","doi":"10.1002/cmdc.202400460","DOIUrl":"https://doi.org/10.1002/cmdc.202400460","url":null,"abstract":"Liquid‐liquid phase separation (LLPS), mediated by G‐quadruplexes (G4s) and intrinsically disordered proteins, particularly those containing RGG domains, plays a critical role in cellular processes and diseases. However, the molecular mechanism and the role of individual amino acid residues of the protein in LLPS with G4 (G4‐LLPS) are still unknown. Here, we systematically designed peptides and investigated the roles of arginine residues in G4‐LLPS. It was found that the FMRP‐derived RGG peptide induced LLPS with G4‐forming Myc‐DNA, whereas a point‐mutated peptide, in which all arginine residues were replaced with lysine, was unable to undergo LLPS, indicating the importance of arginine residues. Moreover, systematically truncated peptides showed that at least five positive net charges of peptide are required to induce G4‐LLPS. Furthermore, quantitative investigation demonstrated that the higher binding affinity of peptides with G4 led to a higher LLPS ability, whereas threshold of the binding affinity for undergoing LLPS was identified. These insights elucidate the pivotal role of arginine in G4‐LLPS and the specific requirement for multiple arginine residues, contributing to a deeper understanding of the complex interplay between intrinsically disordered proteins and nucleic acids.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"24 1","pages":"e202400460"},"PeriodicalIF":3.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201658","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

Phenotypic-Based Discovery and Exploration of a Resorufin Scaffold with Activity against Mycobacterium tuberculosis. 基于表型发现和探索具有抗结核分枝杆菌活性的 Resorufin 支架。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-09 DOI: 10.1002/cmdc.202400482

Eric Tran, Chen-Yi Cheung, Lucy Li, Glen P Carter, Robert W Gable, Nicholas P West, Amandeep Kaur, Yi Sing Gee, Gregory M Cook, Jonathan B Baell, Manuela Jörg

{"title":"Phenotypic-Based Discovery and Exploration of a Resorufin Scaffold with Activity against Mycobacterium tuberculosis.","authors":"Eric Tran, Chen-Yi Cheung, Lucy Li, Glen P Carter, Robert W Gable, Nicholas P West, Amandeep Kaur, Yi Sing Gee, Gregory M Cook, Jonathan B Baell, Manuela Jörg","doi":"10.1002/cmdc.202400482","DOIUrl":"10.1002/cmdc.202400482","url":null,"abstract":"Tuberculosis remains a leading cause of death by infectious disease. The long treatment regimen and the spread of drug-resistant strains of the causative agent Mycobacterium tuberculosis (Mtb) necessitates the development of new treatment options. In a phenotypic screen, nitrofuran-resorufin conjugate 1 was identified as a potent sub-micromolar inhibitor of whole cell Mtb. Complete loss of activity was observed for this compound in Mtb mutants affected in enzyme cofactor F420 biosynthesis (fbiC), suggesting that 1 undergoes prodrug activation in a manner similar to anti-tuberculosis prodrug pretomanid. Exploration of the structure-activity relationship led to the discovery of novel resorufin analogues that do not rely on the deazaflavin-dependent nitroreductase (Ddn) bioactivation pathway for their antimycobacterial activity. These analogues are of interest as they work through an alternative, currently unknown mechanism that may expand our chemical arsenal towards the treatment of this devastating disease.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400482"},"PeriodicalIF":3.6,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152695","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

Cyclodextrin Dimers Functionalized with Biotin as Nanocapsules for Active Doxorubicin Delivery Against MCF-7 Breast Cell Line. 用生物素功能化的环糊精二聚体作为纳米胶囊，可对 MCF-7 乳腺癌细胞株有效释放多柔比星。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-09 DOI: 10.1002/cmdc.202400368

Noemi Bognanni, Chiara Scuderi, Valentina Giglio, Fabio Spiteri, Luana La Piana, Daniele Condorelli, Vincenza Barresi, Graziella Vecchio

{"title":"Cyclodextrin Dimers Functionalized with Biotin as Nanocapsules for Active Doxorubicin Delivery Against MCF-7 Breast Cell Line.","authors":"Noemi Bognanni, Chiara Scuderi, Valentina Giglio, Fabio Spiteri, Luana La Piana, Daniele Condorelli, Vincenza Barresi, Graziella Vecchio","doi":"10.1002/cmdc.202400368","DOIUrl":"10.1002/cmdc.202400368","url":null,"abstract":"Cyclodextrin dimers have been investigated as potential nanocapsules of biomolecules. The presence of two cavities can improve the stability of inclusion complexes, working as a hydrophilic sandwich of poorly water-soluble species. Here, we designed new β- and γ-cyclodextrin dimers functionalized with biotin as a targeting unit and tested the new bioconjugates as doxorubicin delivery systems in cancer cells. Biotin can recognize the Sodium-dependent Multivitamin Transporter (SMVT) receptor, encoded by the Solute Carrier Family 5 Member 6 (SLC5A6) gene and improve the uptake of drugs. We evaluated the expression of the SLC5A6 transcript in human cell lines to select the best cell model (MCF-7) for the in vitro studies. Furthermore, in the cell lines, we investigated the transcript levels of genes correlated to biotin cell availability, Holocarboxylase Synthetase (or HCS encoded by HLCS gene) and Biotinidase (encoded by BTD gene) enzymes. Moreover, the expression of ATP Binding Cassette Subfamily G Member 2 transporter (encoded by ABCG2 gene), which may play a role in doxorubicin resistance, has been investigated. The antiproliferative activity of the doxorubicin complexes with the dimers has been determined to study the effect of the biotin moiety on the cytotoxicity in MCF-7 cancer cells.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400368"},"PeriodicalIF":3.6,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152693","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

Development of Integrin Targeting Chimeras (ITACs) for the Lysosomal Degradation of Extracellular Proteins. 开发用于细胞外蛋白质溶酶体降解的整合素靶向嵌合体 (ITAC)。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-08 DOI: 10.1002/cmdc.202300643

Yaxian Zhou, Yaxian Liao, Yuan Zhao, Weiping Tang

引用次数: 0