Article
Chemistry, Multidisciplinary
Mengxia Sun, Chi Zhang, Dexin Sui, Canchai Yang, Dohun Pyeon, Xuefei Huang, Jian Hu
Summary: Phosphatidylinositol phosphate kinases (PIPKs) are enzymes that produce lipid signaling molecules and have become attractive drug targets for various diseases. Researchers have designed and synthesized D-galactosyl lysophospholipids, which can selectively target phosphatidylinositol 4-phosphate 5-kinase. This study also discovered a human PIKfyve inhibitor that enhances the inhibition of Apilimod, an ATP-competitive PIKfyve inhibitor, in clinical trials for SARS-CoV-2 infection and amyotrophic lateral sclerosis. These findings demonstrate the potential of D-galactose-based phosphoinositide mimetics as artificial substrates and inhibitors of PIPKs.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Medicinal
Francesca Quartieri, Marcella Nesi, Nilla R. Avanzi, Daniela Borghi, Elena Casale, Emiliana Corti, Ulisse Cucchi, Daniele Donati, Marina Fasolini, Eduard R. Felder, Arturo Galvani, Maria L. Giorgini, Antonio Lomolino, Maria Menichincheri, Christian Orrenius, Claudia Perrera, Stefania Re Depaolini, Federico Riccardi-Sirtori, Enea Salsi, Antonella Isacchi, Paola Gnocchi
Summary: This article describes the identification of unprecedented ATP-competitive ChoK alpha inhibitors starting from an initial hit NMS-P830. The structure-based medicinal chemistry program resulted in the discovery of selective compounds with good biochemical activity, solubility, and metabolic stability, suitable for further optimization. The ChoK alpha inhibitors disclosed in this study are the first to demonstrate the potential for inhibiting ChoK alpha with ATP-competitive compounds.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Huabin Hu, Oliver Laufkoetter, Filip Miljkovic, Juergen Bajorath
Summary: Allosteric and ATP-competitive kinase inhibitors act through distinct mechanisms and have different kinase selectivity levels. Despite this, structural analysis revealed that many of these inhibitors contain similar substructures, with some allosteric inhibitors sharing core structures with ATP site-directed inhibitors. Small chemical modifications of common cores can lead to the development of either allosteric or competitive inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Antonino Glaviano, Aaron S. C. Foo, Hiu Y. Lam, Kenneth C. H. Yap, William Jacot, Robert H. Jones, Huiyan Eng, Madhumathy G. Nair, Pooyan Makvandi, Birgit Geoerger, Matthew H. Kulke, Richard D. Baird, Jyothi S. Prabhu, Daniela Carbone, Camilla Pecoraro, Daniel B. L. Teh, Gautam Sethi, Vincenzo Cavalieri, Kevin H. Lin, Nathalie R. Javidi-Sharifi, Eneda Toska, Matthew S. Davids, Jennifer R. Brown, Patrizia Diana, Justin Stebbing, David A. Fruman, Alan P. Kumar
Summary: The PI3K/AKT/mTOR (PAM) signaling pathway plays a crucial role in cell survival, growth, and cell cycle progression. Dysregulation of this pathway is associated with cancer development and resistance to therapy. This review focuses on the major dysregulations in the PAM signaling pathway in cancer and discusses strategies for overcoming treatment resistance. The role of PAM signaling in immunology and immunotherapies is also discussed.
Article
Chemistry, Medicinal
Xufen Yu, Jia Xu, Ling Xie, Li Wang, Yudao Shen, Kaitlyn M. Cahuzac, Xian Chen, Jing Liu, Ramon E. Parsons, Jian Jin
Summary: AKT, a critical node in the PI3K/AKT/m-TOR signaling pathway, is strongly correlated with cancer. Two novel and potent AKT degraders were identified, showing the ability to induce AKT protein degradation and inhibit cancer cell proliferation.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Sandra Roehm, Benedict-Tilman Berger, Martin Schroeder, Deep Chatterjee, Sebastian Mathea, Andreas C. Joerger, Daniel M. Pinkas, Joshua C. Bufton, Amelie Tjaden, Lohitesh Kovooru, Mark Kudolo, Christian Pohl, Alex N. Bullock, Susanne Mueller, Stefan Laufer, Stefan Knapp
Summary: In this study, a potent and cell-active dual DDR/p38 chemical probe was developed, along with a structurally related negative control, for studying DDR kinase signaling. The structure-guided design approach provided insights into the folding process of p38 and how non-conserved amino acids modulate inhibitor selectivity. The developed DDR/p38 probe is a valuable tool for investigating the role of DDR kinase in normal physiology and disease development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Shivani Patel, Vivek K. Vyas, Manmohan Sharma, Manjunath Ghate
Summary: Casein kinase 2 (CK2) is a widely present serine-threonine kinase with diverse functions. It has emerged as a potential drug target for cancer and related disorders. This review provides a comprehensive overview of CK2 protein, its binding pocket, current clinical trial candidates, and structure-guided drug design approaches for CK2 inhibitors. The authors also discuss the importance of CK2 co-crystal structures in facilitating inhibitor discovery.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Martina De Pascale, Lukas Bissegger, Chiara Tarantelli, Florent Beaufils, Alessandro Prescimone, Hayget Mohamed Seid Hedad, Omar Kayali, Clara Orbegozo, Luka Raguz, Thorsten Schaefer, Paul Hebeisen, Francesco Bertoni, Matthias P. Wymann, Chiara Borsari
Summary: The study identifies DHP and THP as isosteres of the morpholine moiety that can be used to generate novel TORKi drugs. Compound 11b is selected as a potent and selective mTOR kinase inhibitor with good metabolic stability and oral bioavailability. In cell experiments, compound 11b demonstrates dose-dependent anti-proliferative activity in splenic marginal zone lymphoma cell lines and synergistic effects with venetoclax.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Horacio Perez-Sanchez, Helena den Haan, Alfonso Perez-Garrido, Jorge Pena-Garcia, Sandipan Chakraborty, Ilkay Erdogan Orhan, Fatma Sezer Senol Deniz, Jose Manuel Villalgordo
Summary: Acetylcholinesterase inhibitors are crucial in treating Alzheimer's disease, and a study identified several potential compounds through drug repurposing screening. Experimental evaluations showed three compounds with high AChE inhibition ability and selectivity, suggesting promising therapeutic potential.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
Alexander Schnitzler, Karsten Niefind
Summary: CK2, a Ser/Thr kinase, has a specific acidic substrate recognition sequence and is inhibited by polyanionic substances like heparin. This study describes the crystal structures of CK2 in complex with different heparin fragments, which provide insights into the inhibitory mechanism of heparin fragments and their chain length-dependent efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Rui Zhang, Heng Li, Xianglei Zhang, Jian Li, Haixia Su, Qiukai Lu, Guangyu Dong, Huixia Dou, Chen Fan, Zhanni Gu, Qianwen Mu, Wei Tang, Yechun Xu, Hong Liu
Summary: A series of novel tetrahydroisoquinoline derivatives were developed and compound 36 exhibited significant inhibitory effects against PDE4D enzymatic activity and TNF-α release, showing more significant efficacy in improving psoriasis-like skin inflammation compared to calcipotriol.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Tong Li, Xianjing Yang, Juan Zhu, Ying Liu, Xiaobao Jin, Gong Chen, Lianbao Ye
Summary: JAK kinase family includes four members: JAK1, JAK2, JAK3, and TYK2. It forms the JAK-STAT pathway with STAT signal transmitters and activators of subscription. This pathway is involved in various immune, inflammatory, and tumor diseases. JAK inhibitors, including pan-JAK inhibitors and selective JAK inhibitors, block the signal transduction of the JAK-STAT pathway and show potential in disease treatment. This review provides an overview of the current application status and advances of JAK inhibitors, as well as the structure-activity relationship, aiming to guide the development of novel JAK inhibitors.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Physical
Wenbo Yu, David J. Weber, Alexander D. MacKerell
Summary: Covalent drug design plays a significant role in drug discovery by forming a covalent bond with targeted residues, leading to a more effective therapeutic approach. Computational methods can identify reactive residues, test potential reactivities, and predict noncovalent contributions to binding. SILCS, a functional group mapping approach, considers protein flexibility, functional group, and protein desolvation along with functional group-protein interactions. SILCS-Covalent, an integrated workflow, can qualitatively and quantitatively inform covalent drug discovery.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Biochemistry & Molecular Biology
Mohamed H. Elsherbeny, Jushin Kim, Noha A. Gouda, Lizaveta Gotina, Jungsook Cho, Ae Nim Pae, Kyeong Lee, Ki Duk Park, Ahmed Elkamhawy, Eun Joo Roh
Summary: A series of novel indole-based small molecules were synthesized as MAO-B inhibitors, with compounds 7b, 8a, 8b, and 8e showing excellent inhibitory effects and selectivity indices, potentially counteracting oxidative stress and displaying safe neurotoxicity profiles in PC12 cells.
Article
Biochemistry & Molecular Biology
Amit Kumar, Kiran Siwach, Claudiu T. Supuran, Pawan K. Sharma
Summary: This study reviews the research in the past decade (2010-2020) focusing on the selective and potent inhibitors of tumor-associated isoforms hCA IX and hCA XII. The tail-approach has been identified as a promising method for designing selective inhibitors.
BIOORGANIC CHEMISTRY
(2022)
Article
Engineering, Electrical & Electronic
Mingsai Huan, Junli Liang, Yifan Wu, Yongkang Li, Wei Liu
Summary: In order to improve the performance of MIMO radar, various sparse arrays have been used. However, the existing nonuniform arrays optimized by combinatorial algorithms or heuristic ones are limited by the Rayleigh criterion, which is related to the aperture size. This research establishes two new models based on the analysis of the angular ambiguity function (AAF), and directly optimizes the sidelobe level (SLL) or the main lobe width (MLW) with the constraints of aperture size and element spacing. Solutions are derived using the alternating direction multiplier method (ADMM), and a hybrid algorithm is proposed to search for the tradeoff between SLL and MLW. Simulations demonstrate the high angular resolution and ambiguity-free properties of the optimized sparse arrays.
IEEE TRANSACTIONS ON ANTENNAS AND PROPAGATION
(2023)
Article
Engineering, Electrical & Electronic
Qiang Li, Lei Huang, Wei Liu, Xinzhu Chen, Lifang Feng
Summary: This work addresses the issue of signal acquisition for a satellite navigation receiver in the presence of outliers using an antenna array. It formulates the acquisition problem as a sparse matrix recovery problem, employing l(2,1)-norms minimization to encourage row sparsity and suppress outliers. Iterative reweighted framework and complex-valued conjugate gradient descent are employed for finding a suitable solution. An improved l(2,1)-norms cost function with composite regularizers is devised to accelerate the convergence rate of mean square error (MSE). Numerical results demonstrate the effectiveness of the proposed methods after downloading actual satellite almanac for providing information on visible satellites.
IEEE TRANSACTIONS ON VEHICULAR TECHNOLOGY
(2023)
Article
Chemistry, Applied
Aaron Baldwin, Shawn Cabral, Kris N. Jones, Jeffrey T. Kohrt, Chris Limberakis, Yiyang Liu, Javier Magano, Sebastien Monfette, Asaad Nematalla, Sami Ovaska, David W. Piotrowski, Jared L. Piper, Jeffrey W. Raggon, Benjamin A. Thuma, Liuqing Wei
Summary: This article discusses the scalable route to PF-07059013 (3), a non-covalent modulator of hemoglobin for the treatment of sickle cell disease. It presents the optimization of the discovery route, including bond connections, late-stage Buchwald-Hartwig C-O coupling, and palladium content reduction strategies. The first process chemistry route to deliver 11 kg of the final API is also discussed.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Chemistry, Medicinal
Wei Liu, Chenggao Wu, Qian Wang, Linju Kuang, Aiping Le
Summary: In this study, the researchers investigated the mechanisms by which Tanshinone IIA (TIIA) affects RA fibroblast-like synoviocytes (RA-FLSs). They used a mouse model of RA called collagen-induced arthritis (CIA) and manipulated matrix metalloproteinase9 (MMP9), receptor for advanced glycation end product (RAGE), and toll-like receptor 9 (TLR9) in both mice and RA-FLSs to study the effects of TIIA. The results showed that TIIA inhibited the proliferation of RA-FLSs, affected autophagy, and improved the symptoms of RA in mice by inhibiting the expression of MMP9 and the activation of TLR9 via the RAGE pathway.
PHYTOTHERAPY RESEARCH
(2023)
Article
Microbiology
Wei Liu, Guang Chen, Keke Dou, Bingcheng Yi, Danyang Wang, Qihui Zhou, Yunbo Sun
Summary: The study investigates the antibacterial activity of eugenol (EG) on carbapenem-resistant Klebsiella pneumoniae (CRKP) and the underlying mechanisms. It is found that EG exhibits dose-dependent inhibitory effects on CRKP by inducing reactive oxygen species (ROS) and reducing glutathione, leading to membrane rupture and leakage of bacterial cytoplasmic components. Moreover, EG can also disrupt the integrity of bacterial biofilm.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Chemistry, Physical
Long Chen, Meng He, Wenbin Gong, Peiying Hu, Shuanglong Yuan, Aiping Chen, Lei Wei, Qichong Zhang, Qingwen Li
Summary: All-inorganic metal halide perovskites (MHPs) have great potential for flexible electronics due to their excellent photo-physical properties and low-cost fabrication. However, their suboptimal quantum yield and stability have hindered their diverse wearable applications. A water evaporation crystallization strategy is proposed to prepare salt-shelled metal halide solids, which exhibit narrow photoluminescence and high quantum yield. These materials can be used in waterborne transparency inks and flexible photoluminescent films, as well as in high-performance positive friction materials for triboelectric nanogenerators. Furthermore, a wearable photoluminescent sensor with voltage response range and quick response time is constructed. These metal halides open up possibilities for lightweight and multifunctional wearable electronics.
Article
Neurosciences
Liuqing Wei, Xueying Li, Lina Huang, Yuansheng Liu, Luming Hu, Wenbin Shen, Qingguo Ding, Pei Liang
Summary: This study used fMRI to investigate the specificity of brain activation when people view circular and angular shapes. The results showed that circular shapes activated the sub-occipital lobe, fusiform gyrus, sub and middle occipital gyrus, and cerebellar VI, while angular shapes activated the cuneus, middle occipital gyrus, lingual gyrus, and calcarine gyrus. The brain activation patterns of circular shapes did not differ significantly from those of angular shapes, contradicting previous research on cross-modal correspondence of shape curvature. The different brain regions detected by circular and angular shapes and their potential explanations were discussed in the paper.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Nanoscience & Nanotechnology
Yuntian Wang, Zhixun Wang, Zhe Wang, Ting Xiong, Perry Ping Shum, Lei Wei
Summary: The integration of functional fibers into wearable devices by traditional methods is commonly completed in weaving. A new post-weaving method of integrating fiber devices into textiles is needed to address the challenge of incorporating functional fiber into ready-made garments without tearing down the clothing and re-weaving. A 3D printing method is presented to simultaneously fabricate and integrate highly stretchable conductive fiber into ready-made garments with designed patterns, showing the potential applications in wearable electronics.
ADVANCED ELECTRONIC MATERIALS
(2023)
Article
Food Science & Technology
Dantong Li, Taotao Dai, Mingshun Chen, Ruihong Liang, Wei Liu, Chengmei Liu, Jian Sun, Jun Chen, Lizhen Deng
Summary: The study investigated the changes in quality and volatile properties of mangoes at different ripening stages during infrared drying. Results showed variations in total soluble solids/titratable acid, texture, nutrient composition, and volatile compounds during drying. Fruits at RS-3 stage exhibited the highest increase in total phenolic content, the most dramatic decrease in vitamin C content, and the lowest decrease in beta-carotenoid contents. The evaluation score at RS-3 was the highest among all stages, indicating its superior quality.
Article
Chemistry, Physical
Wei Guo, Ben Li, Haijun Chi, Zhongliang Jiang, Liu Qing Wei, Edward D. Ramsey
Summary: Two flow selection interfaces were developed for connecting reactors with on-line SFC-DAD-MS, enabling the study of reactions in SF-CO2. Different reactions in SF-CO2 were monitored, including electrophilic annulation reactions with three amine reactants and a two-step synthetic procedure. The use of on-line SFC-DAD-MS facilitated the early detection and characterization of unexpected by-products.
JOURNAL OF SUPERCRITICAL FLUIDS
(2023)
Article
Engineering, Electrical & Electronic
Zixiang Yang, Qing Shen, Wei Liu, Yonina C. C. Eldar, Wei Cui
Summary: In this work, fractal arrays were proposed for exploiting the 2qth-order difference co-array. The robustness and mutual coupling leakage of the 2qth-O-Fractal framework were analyzed. The results showed that the robustness of 2qth-O-Fractal could be improved by designing a robust generator or increasing the fractal order. The mutual coupling leakage of 2qth-O-Fractal was also upper bounded by that of its generator array. Simulation results demonstrated the superior performance of the proposed 2qth-O-Fractal over existing structures.
IEEE TRANSACTIONS ON SIGNAL PROCESSING
(2023)
Review
Green & Sustainable Science & Technology
Qian Cai, Wenting Hong, Chuanyong Jian, Xu He, Wei Liu
Summary: This review article comprehensively summarizes the current issues of electrocatalysts for alkaline hydrogen evolution reaction (HER) with high current density. It provides design principles and critical factors for preparing high-performance electrocatalysts, and presents the recent advances in self-supported transition metal-based electrocatalysts. The article aims to guide the rational design of self-supported high-current density electrocatalysts for future commercial hydrogen production.
ADVANCED ENERGY AND SUSTAINABILITY RESEARCH
(2023)
Article
Geochemistry & Geophysics
Huaping Xu, Guobing Zeng, Wei Liu, Yuan Wang
Summary: Multitemporal synthetic aperture radar interferometry (MTInSAR) is an efficient geodetic tool for measuring Earth surface displacement. The polarimetric capability of SAR satellites offers an opportunity to improve MTInSAR phase series estimation. In this study, a maximum likelihood estimator for multipolarimetric phase linking (MLE-MPPL) is proposed. The experimental results show that MLE-MPPL achieves the best estimation performance and is more robust against interchannel interference than existing methods.
IEEE TRANSACTIONS ON GEOSCIENCE AND REMOTE SENSING
(2023)
Article
Green & Sustainable Science & Technology
Yang Ban, Ying Wang, Xiaohong Chen, Liuqing Wei
Summary: Regional economic efficiency and resilience are essential for sustainable regional economic development, with urban agglomerations playing a crucial role. Understanding the synergistic patterns between economic efficiency and resilience is key to promoting the sustainable growth of urban agglomerations and their surrounding areas.
Review
Materials Science, Multidisciplinary
Dan Zhu, Zhenyu Zhang, Min Chen, Pan Li, Yuanzhuo Xiang, Jingyu Ouyang, Zhiheng Huang, Xiaojuan Liu, Fuhong Wang, Maiping Yang, Hongtao Zeng, Ping Hong, Lei Wei, Chong Hou, Guangming Tao
Summary: This paper proposes an advanced performance analysis system powered by intelligent fabric for rhythmic gymnasts. The system uses intelligent fabric to detect physiological and anthropometric data, and employs artificial intelligence techniques for behavior recognition and decision-making, providing personalized suggestions. Additionally, four typical applications are presented to improve training performance.
ADVANCED FIBER MATERIALS
(2023)
