Article
Cell Biology
Sinu P. John, Anju Singh, Jing Sun, Makheni Jean Pierre, Lulwah Alsalih, Crystal Lipsey, Ziann Traore, Shenavia Balcom-Luker, Clinton J. Bradfield, Jian Song, Tovah E. Markowitz, Margery Smelkinson, Marc Ferrer, Iain D. C. Fraser
Summary: Biologically active small molecules can modulate cellular responses in macrophages, enhancing inflammatory cytokine secretion and increasing resistance to viral infections. These molecules, such as rutaecarpine and SYKi IV, have potential applications in prophylactic treatments for viral susceptibility.
Article
Chemistry, Medicinal
Donghwa Kim, Sang Won Choi, Jihee Cho, Jae-Hui Been, Kyoungsun Choi, Wenzhe Jiang, Jaeho Han, Jedo Oh, Changmin Park, Soongyu Choi, Songyi Seo, Koung Li Kim, Wonhee Suh, Sang Kook Lee, Sanghee Kim
Summary: Diabetic retinopathy is a leading cause of blindness associated with excessive angiogenesis. Researchers have developed a novel antiangiogenesis agent by modifying the structure of wondonin marine natural products, resulting in improved bioactivity and selectivity. This compound, 31, shows potential as a lead for developing small-molecule drugs to treat diabetic retinopathy and to uncover new mechanisms of angiogenesis.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Tangting Chen, Haiyan Zhou, Shuangshuang Yuan, Xin Deng, Yongjie Li, Ni Chen, Jingcan You, Rong Li, Tian Li, Youkun Zheng, Mao Luo, Hongbin Lv, Jianbo Wu, Liqun Wang
Summary: Glycation of fibronectin (FN) can impair the Ang-1/Tie-2 signaling pathway, leading to a dysfunction in angiogenesis and cell survival. This may provide a molecular mechanism for the dysfunction of Ang-1/Tie-2 signaling and angiogenesis failure in diabetic ischemic diseases.
CELLULAR SIGNALLING
(2023)
Article
Biochemistry & Molecular Biology
Haiyan Zhou, Tangting Chen, Yongjie Li, Jingcan You, Xin Deng, Ni Chen, Tian Li, Youkun Zheng, Rong Li, Mao Luo, Jianbo Wu, Liqun Wang
Summary: This study found that Tie-2 is modified by AGEs in diabetes, leading to the inhibition of Ang-1 signaling activation and angiogenesis. This finding provides a novel mechanism for Ang-1/Tie-2 signal dysfunction and angiogenesis failure in diabetic ischemic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Amelie Marguier, Caroline Laheurte, Benoit Lecoester, Marine Malfroy, Laura Boullerot, Adeline Renaudin, Evan Seffar, Abhishek Kumar, Charlee Nardin, Francois Aubin, Olivier Adotevi
Summary: This study investigates a novel subset of monocytic MDSCs called TIE-2(+) M-MDSCs in melanoma patients. These cells show a highly immunosuppressive phenotype and are associated with the pro-angiogenic factor ANGPT2. The study demonstrates that exposure to ANGPT2 increases the immune suppressive function of TIE-2(+) M-MDSCs and that active TIE-2 signaling is required for optimal suppressive activity. This suggests that the TIE-2(+) M-MDSC/ANGPT2 axis may play a role in immune escape in melanoma.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Wei Yang, Bo Mu, Jing You, Chenyu Tian, Huachao Bin, Zhiqiang Xu, Liting Zhang, Ronggang Ma, Ming Wu, Guo Zhang, Chong Huang, Linli Li, Zhenhua Shao, Lunzhi Dai, Laurent Desaubry, Shengyong Yang
Summary: In this study, a new non-classical ferroptosis inhibitor YL-939 was discovered, which binds to PHB2 and promotes the expression of ferritin, thereby reducing iron content and decreasing susceptibility to ferroptosis. The authors also showed that YL-939 can ameliorate liver damage in an acute liver injury model by targeting the PHB2/ferritin/iron axis. These findings reveal a new regulation mechanism of ferroptosis and present an attractive intervention strategy for ferroptosis-related diseases.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Michal Otreba, Johanna Johansson Sjolander, Morten Grotli, Per Sunnerhagen
Summary: The small molecule INR119 enhances the activity of protein kinases in fission yeast and human cells under oxidative stress, with a potential conservation of its mechanism of action between yeast and humans.
Article
Oncology
Jing Yang, Ellen L. Weisberg, Xiaoxi Liu, Robert S. Magin, Wai Cheung Chan, Bin Hu, Nathan J. Schauer, Shengzhe Zhang, Ilaria Lamberto, Laura Doherty, Chengcheng Meng, Martin Sattler, Lucia Cabal-Hierro, Eric Winer, Richard Stone, Jarrod A. Marto, James D. Griffin, Sara J. Buhrlage
Summary: The study identified a strategy to target mutated JAK2 protein for degradation using the cell's intracellular degradation machinery. It also validated the mechanism of deubiquitinase JOSD1 interacting with mutant JAK2, providing a novel therapeutic approach to selectively target mutated JAK2 signaling in myeloproliferative neoplasms (MPN).
Review
Chemistry, Medicinal
Lixin Zhou, Tianyu Wang, Kuojun Zhang, Xiangyu Zhang, Sheng Jiang
Summary: Hematopoietic progenitor kinase 1 (HPK1) is a serine/threonine protein kinase that negatively regulates T cells, B cells, and dendritic cells-mediated immune responses. It plays a role in cellular processes such as immune cell activation, differentiation, proliferation, adhesion, and apoptosis. HPK1 is associated with the occurrence and development of human malignant tumors, making it a promising target for cancer immunotherapies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Zhouling Xie, Xiaoxiao Yang, Yajun Duan, Jihong Han, Chenzhong Liao
Summary: Kinase inhibitors have been successful in treating various diseases beyond cancer, including autoimmune diseases and inflammatory diseases. Several non-oncologic small-molecule kinase inhibitors have been approved, with more in development for different applications.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Anirban Das, Yogesh M. Gangarde, Ranit Pariary, Anirban Bhunia, Ishu Saraogi
Summary: This article introduces a novel amphiphilic molecule called PAD-S, which acts as a chemical chaperone to completely inhibit the fibrillation of insulin and its biosimilars. PAD-S can bind to the key hydrophobic regions of insulin, preventing its self-assembly and protecting cells from insulin amyloid-induced cytotoxicity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Biochemistry & Molecular Biology
Linwei Li, Songtao Liu, Bi Wang, Fei Liu, Shu Xu, Pirui Li, Yu Chen
Summary: Small molecule kinase inhibitors (SMKIs) play a crucial role in drug research and development, with numerous approved drugs and candidates in clinical trials. Computer-aided drug design (CADD) is essential in the discovery and optimization of SMKIs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pathology
Ying Zhang, Shoufang Xu, Feiyu Jiang, Mengsi Hu, Yetao Han, Yingjian Wang, Zhiwei Liu
Summary: Angiogenesis is a critical factor in the development of solid tumors and hematological malignancies, but its impact on molecular pathways in malignancies remains unclear. The angiopoietin family, specifically Angiogenin and Tie, have been studied for their diagnostic, prognostic, and therapeutic potential. This review focuses on the function of the molecular pathways affected by the Angiogenin and Tie system in hematological malignancies.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Review
Peripheral Vascular Disease
Ferdinand A. C. le Noble, Jean-Jacques Mourad, Bernard I. Levy, Harry A. J. Struijker-Boudier
Summary: Drugs inhibiting VEGF have been widely used in cancer treatment, but they often cause cardiovascular side effects, with hypertension being the most frequently observed. This review explores the mechanism behind VEGF inhibitor-induced hypertension, focusing on microvascular rarefaction, which is supported by evidence from experimental and clinical studies.
Article
Biochemistry & Molecular Biology
Shunsuke Sawada, Masaru Yoshikawa, Keita Tsutsui, Tomoki Miyazaki, Keiko Kano, Emi Mishiro-Sato, Shinya Tsukiji
Summary: Small-molecule fluorescent probes based on the myrGC3Me motif were developed for simple and rapid staining of the Golgi in living cells with high specificity and no cytotoxicity. The probes allowed visualization of dynamic changes of the Golgi morphology induced by drug treatments and during cell division. These probes are useful tools for cell biological and diagnostic applications.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Simon Boothroyd, Andy Kerridge, Anders Broo, David Buttar, Jamshed Anwar
CRYSTAL GROWTH & DESIGN
(2018)
Article
Chemistry, Medicinal
James S. Scott, Andrew Bailey, David Buttar, Rodrigo J. Carbajo, Jon Curwen, Paul R. J. Davey, Robert D. M. Davies, Sebastien L. Degorce, Craig Donald, Eric Gangl, Ryan Greenwood, Sam D. Groombridge, Tony Johnson, Scott Lamont, Mandy Lawson, Andrew Lister, Christopher J. Morrow, Thomas A. Moss, Jennifer H. Pink, Radoslaw Polanski
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Stephanie M. Myers, Duncan C. Miller, Lauren Molyneux, Mercedes Arasta, Ruth H. Bawn, Timothy J. Blackburn, Simon J. Cook, Noel Edwards, Jane A. Endicott, Bernard T. Golding, Roger J. Griffin, Tim Hammonds, Ian R. Hardcastle, Suzannah J. Harnor, Amy B. Heptinstall, Pamela A. Lochhead, Mathew P. Martin, Nick C. Martin, David R. Newell, Paul J. Owen, Leon C. Pang, Tristan Reuillo, Laurent J. M. Rigoreau, Huw D. Thomas, Julie A. Tucker, Lan-Zhen Wang, Ai-Ching Wong, Martin E. M. Noble, Stephen R. Wedge, Celine Cano
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Stephan Wilmes, Maximillian Hafer, Joni Vuorio, Julie A. Tucker, Hauke Winkelmann, Sara Loechte, Tess A. Stanly, Katiuska D. Pulgar Prieto, Chetan Poojari, Vivek Sharma, Christian P. Richter, Rainer Kurre, Stevan R. Hubbard, K. Christopher Garcia, Ignacio Moraga, Ilpo Vattulainen, Ian S. Hitchcock, Jacob Piehler
Article
Multidisciplinary Sciences
Pamela A. Lochhead, Julie A. Tucker, Natalie J. Tatum, Jinhua Wang, David Oxley, Andrew M. Kidger, Victoria P. Johnson, Megan A. Cassidy, Nathanael S. Gray, Martin E. M. Noble, Simon J. Cook
NATURE COMMUNICATIONS
(2020)
Review
Biochemistry & Molecular Biology
Simon J. Cook, Julie A. Tucker, Pamela A. Lochhead
BIOCHEMICAL SOCIETY TRANSACTIONS
(2020)
Editorial Material
Biochemistry & Molecular Biology
Julie A. Tucker, Mathew P. Martin
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Ian S. Hitchcock, Maximillian Hafer, Veena Sangkhae, Julie A. Tucker
Summary: Thrombopoietin (TPO) and its receptor MPL play essential roles in platelet production and hematopoietic stem cell maintenance, with dysregulation contributing to hematological disorders; abnormalities in the TPO-MPL axis can lead to bone marrow failure or pathological myeloproliferation; recent resolution of the debate over how TPO binding activates MPL holds potential for better-targeted therapies in blood disorders.
Article
Biochemical Research Methods
Helen S. Beeston, Tobias Klein, Richard A. Norman, Julie A. Tucker, Malcolm Anderson, Alison E. Ashcroft, Geoffrey A. Holdgate
Summary: This study utilized X-ray crystallography and biochemical methods to determine the binding modes of type I and type II kinase inhibitors with FGFR1, and demonstrated distinct differences in the folding landscape of FGFR1 for the two types of inhibitors using ESI-IMS-MS technology. The results suggest that conformational variations detected by ESI-IMS-MS can effectively distinguish between type I and type II inhibitors, providing a rapid and high-throughput screening method for novel kinase inhibitors.
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
(2021)
Article
Chemistry, Organic
James J. Douglas, Matthew R. Tatton, Daniel de Bruin, David Buttar, Calum Cook, Kuangchu Dai, Catalina Ferrer, Kevin Leslie, James Morrison, Rachel Munday, Thomas O. Ronson, Hucheng Zhao
Summary: In this study, route design and synthesis of a challenging chirally atropisomeric inhibitor were conducted to improve synthesis efficiency and avoid racemization. The strategy was further validated on other substrates.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Frederick W. Goldberg, Jason G. Kettle, Gillian M. Lamont, David Buttar, Attilla K. T. Ting, Thomas M. McGuire, Calum R. Cook, David Beattie, Pablo Morentin Gutierrez, Stefan L. Kavanagh, Jasper C. Komen, Aarti Kawatkar, Roger Clark, Lorna Hopcroft, Gareth Hughes, Susan E. Critchlow
Summary: Due to increased reliance on glycolysis, monocarboxylate transporters (MCTs) are upregulated in cancer. MCT4 inhibition can lead to cytotoxic levels of intracellular lactate and may be of interest for immuno-oncology. A triazolopyrimidine hit was identified as a potential MCT4 inhibitor, and further modifications were made to improve potency, selectivity, and other properties. The resulting clinical candidate 15 (AZD0095) has excellent potency, MCT1 selectivity, clean mechanism of action, suitable properties for oral administration, and good preclinical efficacy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Nadim Akhtar, Marianne B. Ashford, Louisa Beer, Alex Bowes, Tony Bristow, Anders Broo, David Buttar, Steve Coombes, Rebecca Cross, Emma Eriksson, Jean-Baptiste Guilbaud, Stephen W. Holman, Leslie P. Hughes, Mark Jackman, M. Jayne Lawrence, Jessica Lee, Weimin Li, Rebecca Linke, Najet Mahmoudi, Marc McCormick, Bryce MacMillan, Ben Newling, Maryann Ngeny, Claire Patterson, Andy Poulton, Andrew Ray, Natalie Sanderson, Silvia Sonzini, Yayan Tang, Kevin E. Treacher, Dave Whittaker, Stephen Wren
Summary: The recent emergence of drug-dendrimer conjugates presents analytical and measurement challenges in the pharmaceutical industry. These complex molecules have high molecular weights and diverse characteristics. The understanding and definition of their characteristics and quality attributes, which impact efficacy and safety, require measurement of molecular weight, impurity characterization, quantification of conjugated versus free API molecules, determination of impurity profiles, primary structure, particle size, and morphology. This study provides a global characterization of a drug-dendrimer conjugate and discusses the impact of various analytical and measurement techniques on understanding this complex molecular entity. The results are crucial for the future development of dendrimer-based medicines.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Polymer Science
R. M. England, S. Sonzini, D. Buttar, K. E. Treacher, M. B. Ashford
Summary: This study characterized poly(l-lysine) dendrimers using advanced analytical techniques and molecular dynamics simulations. The results showed an increase in refractive index and intrinsic viscosity in the early generations of the dendrimers, which decreased in later generations. The protected dendrimers had different molecular density profiles compared to the unprotected dendrimers, possibly due to electrostatic repulsion. This research provides valuable insights into the structure and properties of PLL dendrimers for drug delivery applications.
Article
Chemistry, Multidisciplinary
Kjell Jorner, Tore Brinck, Per-Ola Norrby, David Buttar
Summary: The study introduces hybrid models combining traditional transition state modeling and machine learning to accurately predict reaction barriers, offering competitive accuracy in low-data scenarios.
Article
Chemistry, Multidisciplinary
Amol Thakkar, Simon Johansson, Kjell Jorner, David Buttar, Jean-Louis Reymond, Ola Engkvist
Summary: The article discusses the development of synthesis planning technologies and the relevance of computer-assisted synthesis planning (CASP) in drug discovery and development. It emphasizes the need for an automated synthesis platform to enhance chemical workflows, and highlights the interaction between experimental and computational scientists as a key driver of technological development.
REACTION CHEMISTRY & ENGINEERING
(2021)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
