ChemMedChem最新文献_第9页

Corrin Ring Modification in Peptide Drug Development – a Brief History of “Corrination” 肽药物开发中的科林斯环偶联-“科林斯”简史。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-13 DOI: 10.1002/cmdc.202500129

Nancy Cham, Robert P. Doyle

{"title":"Corrin Ring Modification in Peptide Drug Development – a Brief History of “Corrination”","authors":"Nancy Cham, Robert P. Doyle","doi":"10.1002/cmdc.202500129","DOIUrl":"10.1002/cmdc.202500129","url":null,"abstract":"Recently, the term “corrination” was coined to describe the conjugate modification of a peptide, protein, small molecule, or radionuclide with a corrin ring-containing molecule. By exploiting the innate chemicophysical properties of corrin ring-containing compounds, corrination has been explored for drug development and targeted/localized delivery of probes and therapeutics. Most recently, it is in the field of peptide-based therapeutics that corrination is generating significant interest. Peptide-based drugs possess several limitations that restrict their clinical application, including poor solubility and stability, low oral bioavailability, and negative side effects often due to drug distribution. In this mini review, the design and synthetic approaches to peptide corrination are described, along with examples of in vitro, ex vivo, and in vivo biological evaluations of corrinated conjugates, which demonstrate the broad applicability of the technique, namely 1) mitigated peptide aggregation, 2) improved protection against proteolysis, 3) reduced negative side effects via targeted localization, 4) regioselective production of peptide disulfide bonds, and 5) improved oral drug absorption. Herein, it is described how corrination offers a facile route to improving peptide pharmacokinetic and pharmacodynamic properties, making this a useful platform technology in the field of peptide drug development.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202500129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622930","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

Significant Tumor Inhibition of Trimethyl-152-[L-aspartyl]pheophorbide a in Tumor Photodynamic Therapy≠ 三甲基-152-[l-天冬氨酸]酚a在肿瘤光动力治疗中的显著肿瘤抑制作用

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-12 DOI: 10.1002/cmdc.202500087

Anita Benić, Akmaral Kussayeva, Ivana Antol, Mario Vazdar, Zlatko Brkljača, Dan-Ye Chen, Yi-Jia Yan, Ying-Hua Gao, Zhi-Long Chen, Davor Margetić

引用次数: 0

Boron in My Mind: A Comprehensive Review of the Evolution of the Diverse Syntheses of 4-Borono-l-Phenylalanine, the Leading Agent for Boron Neutron Capture Therapy 我心目中的硼：硼中子俘获治疗的先导剂4-硼-l-苯丙氨酸的多种合成演变的综合综述。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-12 DOI: 10.1002/cmdc.202500059

Sarfraz Ahmad, Ming Pan, John J. Hayward, Massimo Sementilli, Lisa A. Porter, John F. Trant

{"title":"Boron in My Mind: A Comprehensive Review of the Evolution of the Diverse Syntheses of 4-Borono-l-Phenylalanine, the Leading Agent for Boron Neutron Capture Therapy","authors":"Sarfraz Ahmad, Ming Pan, John J. Hayward, Massimo Sementilli, Lisa A. Porter, John F. Trant","doi":"10.1002/cmdc.202500059","DOIUrl":"10.1002/cmdc.202500059","url":null,"abstract":"Boron neutron capture therapy leverages the nuclear reaction between boron-10 and thermal neutrons to selectively destroy cancer cells while minimizing damage to surrounding healthy tissues. This therapy finds use in treating glioblastoma, which, as a brain cancer, is difficult to treat using conventional radiotherapy, surgery, and chemotherapy due to location and the risk of brain damage. However, to work, the cells must contain 10B. 4-Borono-l-phenylalanine (l-BPA) is the most frequently used boron delivery agent in this therapy. Surprisingly, despite its seemingly simple structure, there is no consensus approach to making it—the synthesis of l-BPA has been approached through multiple routes, reflecting the challenges in producing high-purity, isotopically enriched material. When a new site is looking to make this essential material, it can be challenging to determine the best route for the situation as there is no critical analysis comparing and discussing the relative merits of the approaches. Herein, the reported methods, from both the academic and patent literature, used to synthesize l-BPA, are comprehensively and critically examined and compared. The review also highlights the limitations of each method regarding scalability, cost-effectiveness, and safety, especially considering the high cost of isotopically enriched 10B.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202500059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612946","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

Discovery of Galactopyranose-1-carboxamides as a New Class of Small, Novel, Potent, Selective, and Orally Active Galectin-3 Inhibitors 半乳糖丙酮糖-1-羧酰胺类小、新型、有效、选择性和口服活性半乳糖凝集素-3抑制剂的发现。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-12 DOI: 10.1002/cmdc.202401012

Dr. Cornelia Zumbrunn, Dr. Luboš Remen, Dr. Christoph P. Sager, Dr. Corinna Grisostomi, Christina Stamm, Daniela Krüsi, Sven Glutz, Dr. Gunther Schmidt, Dr. Oliver Nayler, Dr. Marc Iglarz, Dr. Aengus Mac Sweeney, Alain Chambovey, Manon Müller, Celia Mueller, Geoffroy Bourquin, Dr. Solange Meyer, Dr. Eva Hühn, Christophe Cattaneo, Dr. Magali Vercauteren, Dr. John Gatfield, Dr. Martin H. Bolli

{"title":"Discovery of Galactopyranose-1-carboxamides as a New Class of Small, Novel, Potent, Selective, and Orally Active Galectin-3 Inhibitors","authors":"Dr. Cornelia Zumbrunn, Dr. Luboš Remen, Dr. Christoph P. Sager, Dr. Corinna Grisostomi, Christina Stamm, Daniela Krüsi, Sven Glutz, Dr. Gunther Schmidt, Dr. Oliver Nayler, Dr. Marc Iglarz, Dr. Aengus Mac Sweeney, Alain Chambovey, Manon Müller, Celia Mueller, Geoffroy Bourquin, Dr. Solange Meyer, Dr. Eva Hühn, Christophe Cattaneo, Dr. Magali Vercauteren, Dr. John Gatfield, Dr. Martin H. Bolli","doi":"10.1002/cmdc.202401012","DOIUrl":"10.1002/cmdc.202401012","url":null,"abstract":"Galectin-3 (Gal-3), a β-galactoside-binding lectin, is implicated in diverse cellular functions ranging from immune response modulation to tissue homeostasis. Notably, increased Gal-3 expression has been linked to the progression of numerous diseases, including cancer, fibrosis, and cardiovascular disorders, underscoring its potential as a therapeutic target. Small molecule inhibitors have been discovered and are valuable tools to study such diseases. We report here the discovery of novel, galactose-based, small molecule inhibitors such as compound 12 which are orally bioavailable and show efficacy in a mouse model of acute liver injury and fibrosis (CCl4 model). The use of structure-based drug design (docking of a virtual library of amides based on acid 2) was key in the process towards potent, nanomolar inhibitors.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602989","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

Isoniazid-Dihydropyrimidinone Molecular Hybrids: Design, Synthesis, Antitubercular Activity, and Cytotoxicity Investigations with Computational Validation 异烟肼-二氢嘧啶分子杂合体：设计、合成、抗结核活性和细胞毒性研究与计算验证。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-11 DOI: 10.1002/cmdc.202400949

Gobind Kumar, Pule Seboletswe, Sahil Mishra, Neha Manhas, Safiyah Ghumran, Nagaraju Kerru, Françoise Roquet-Banères, Maëlle Foubert, Laurent Kremer, Gaurav Bhargava, Parvesh Singh

{"title":"Isoniazid-Dihydropyrimidinone Molecular Hybrids: Design, Synthesis, Antitubercular Activity, and Cytotoxicity Investigations with Computational Validation","authors":"Gobind Kumar, Pule Seboletswe, Sahil Mishra, Neha Manhas, Safiyah Ghumran, Nagaraju Kerru, Françoise Roquet-Banères, Maëlle Foubert, Laurent Kremer, Gaurav Bhargava, Parvesh Singh","doi":"10.1002/cmdc.202400949","DOIUrl":"10.1002/cmdc.202400949","url":null,"abstract":"A new series of isoniazid-dihydropyrimidinone molecular hybrids (8a–8n) were designed, synthesized and structurally characterized using different spectroscopic techniques viz., Fourier transform infrared spectroscopy, nuclear magnetic resonance (NMR), and high-resolution mass spectrometry followed by their antitubercular evaluation including their precursors (4a–4n), and a standard antitubercular drug (isoniazid; INH). The molecular hybrids particularly 8g (minimum inhibitory concentration (MIC) = 6.25 μg mL−1), 8h (MIC = 1.56 μg mL−1), 8k (MIC = 0.78 μg mL−1), 8l (MIC = 6.25 μg mL−1), and 8n (MIC = 0.39 μg mL−1) demonstrated the most potent inhibitory activity against wild-type M. tuberculosis mc26230, disclosing 8n as the most potent compound in the series. However, the potent compounds lost their activity against three INH-resistant M. tuberculosis strains mutated in katG. The more efficient compounds (8h, 8k, and 8n) were subsequently evaluated for their cytotoxicity against the THP-1 human monocytic cell line. Furthermore, the stability studies of the most potent compound carried out using 1H NMR, UV-visible, and liquid chromatography-mass spectrometry revealed their structural integrity. Finally, in silico molecular docking simulations were conducted to explore the binding orientations of the potent compounds in the active site of the target protein InhA while ADME/T (absorption, distribution, metabolism, excretion, and toxicity) and global reactivity parameters were explored to determine their drug-likeness and stability profiles, respectively.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202400949","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603007","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

Ergosterol and Lanosterol Derivatives: Synthesis and Possible Biomedical Applications 麦角甾醇和羊毛甾醇衍生物：合成和可能的生物医学应用。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-09 DOI: 10.1002/cmdc.202400948

Joanna Stefaniak-Skorupa, MSc. Prof. Maria J. Milewska

引用次数: 0

Methods for the Generation of Single-Payload Antibody-Drug Conjugates 单载荷抗体-药物偶联物的制备方法。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-07 DOI: 10.1002/cmdc.202500132

Dr. Thomas Wharton, Prof. David R. Spring

引用次数: 0

Front Cover: Carbon-13 Hyperpolarization of α-Ketocarboxylates with Parahydrogen in Reversible Exchange (ChemMedChem 5/2025) 封面：可逆交换中α-酮羧酸酯与对氢的碳-13超极化（ChemMedChem 5/2025）

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-06 DOI: 10.1002/cmdc.202580501

Stephen J. McBride, Keilian MacCulloch, Patrick TomHon, Austin Browning, Samantha Meisel, Mustapha Abdulmojeed, Boyd M. Goodson, Eduard Y. Chekmenev, Thomas Theis

引用次数: 0

Cover Feature: Current Context of Designing Phototheranostic Cyclometalated Iridium (III) Complexes to Open a New Avenue in Cancer Therapy (ChemMedChem 5/2025) 封面特写：设计光疗环金属化铱（III）配合物为癌症治疗开辟新途径的当前背景（ChemMedChem 5/2025）

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-06 DOI: 10.1002/cmdc.202580502

Sreelekha U, Uttara Basu, Prof. Priyankar Paira

{"title":"Cover Feature: Current Context of Designing Phototheranostic Cyclometalated Iridium (III) Complexes to Open a New Avenue in Cancer Therapy (ChemMedChem 5/2025)","authors":"Sreelekha U, Uttara Basu, Prof. Priyankar Paira","doi":"10.1002/cmdc.202580502","DOIUrl":"https://doi.org/10.1002/cmdc.202580502","url":null,"abstract":"The cover art features an iridium complex with distinct cyclometalated ligands that enhance both bioimaging and therapeutic properties. The illustration also highlights the therapeutic function, where the iridium complex, upon light irradiation, induces apoptosis or cellular damage, representing its targeted cancer-fighting capabilities. The review article presents the current advancements and future potential of cyclometalated iridium (III) complexes as a phototheranostic agent. The finding demonstrates that cyclometalated iridium (III) complexes hold significant promise for both bioimaging and therapeutic purposes, showcasing potent anticancer activity that addresses the limitations of conventional cancer therapies by enabling more effective targeted delivery. More details can be found in article 10.1002/cmdc.202400649 by Priyankar Paira and co-workers.<figure>\u0000 <div><picture>\u0000 <source></source></picture>\u0000 </div>\u0000 </figure>\u0000 ","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202580502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565056","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

Signaling Pathways and Promising Small-Molecule Therapeutic Agents for Ischemic Stroke 缺血性卒中的信号通路和有前途的小分子治疗药物。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-02 DOI: 10.1002/cmdc.202400975

Debasis Das, Yimeng Wu, Jian Hong

{"title":"Signaling Pathways and Promising Small-Molecule Therapeutic Agents for Ischemic Stroke","authors":"Debasis Das, Yimeng Wu, Jian Hong","doi":"10.1002/cmdc.202400975","DOIUrl":"10.1002/cmdc.202400975","url":null,"abstract":"Stroke is the second highest cause of death and leading cause of disability with high economic burden worldwide. The incidence of stroke is increasing faster and more prevalent for the global population over age 65. Ischemic stroke (IS) has a higher incidence than hemorrhagic stroke, accounting over 80 % of the total incidence of stroke. The rate of ischemic stroke is increasing in all age groups and both sexes. In present era, hypertension, high blood pressure and modern lifestyle are considered as the causes of the disease. The treatment options for stroke is still limited, mainly thrombolytic and thrombectomy therapy are available options. In the past decade, a number of therapeutic agents have been studied for the acute ischemic stroke to protect the brain from ischemic injury. Several study methods focus to improve neurons functions around the ischemic core and protect from the shock. Many signalling pathways including NF-kB, NrF, Nrf2-Keap1, PI3K/AKT, JAK/STAT signalling pathways are strongly associated for the indication. Controlling the signalling pathways by small molecules potentially improve the neuronal functions. In this article, we review the recent advancement of the drug discovery, controlling the signalling pathways by small molecules, and kinase inhibitors in ischemic stroke.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536278","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