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BPS2025 - Structural basis of potassium selectivity in kalium channelrhodopsins

Biophysical Journal 2025年第3期124卷 64a-65a页

作者： Seiya Tajima Yoon Seok Kim YoungJu Jo Peter Y. Wang Joseph M. Paggi Charu Ramakrishnan Shunki Takaramoto Takashi Nagata Masae Konno Kota Katayama Hideki Kandori Ron O. Dror Keiichi Inoue Karl Deisseroth Hideaki Kato Research Center for Advanced Science and Technology The University of Tokyo Tokyo Japan Department of Bioengineering Stanford University Stanford CA USA Department of Computer Science Stanford University Stanford CA USA Cracking the Neural Code Program Stanford University Stanford CA USA The Institute for Solid State Physics The University of Tokyo Kashiwa Japan PRESTO Japan Science and Technology Agency Kawaguchi Japan Department of Life Science and Applied Chemistry Nagoya Institute of Technology Nagoya Japan OptoBioTechnology Research Center Nagoya Institute of Technology Nagoya Japan Institute for Computational and Mathematical Engineering Stanford University Stanford CA USA Howard Hughes Medical Institute Stanford University Stanford CA USA Graduate School of Arts and Sciences The University of Tokyo Tokyo Japan

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Fast, accurate, and versatile data analysis platform for the quantification of molecular spatiotemporal signals

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Cell 2025年第10期188卷 2794-2809.e21页

作者： Mi, Xuelong Chen, Alex Bo-Yuan Duarte, Daniela Carey, Erin Taylor, Charlotte R. Braaker, Philipp N. Bright, Mark Almeida, Rafael G. Lim, Jing-Xuan Ruetten, Virginia M.S. Wang, Yizhi Wang, Mengfan Zhang, Weizhan Zheng, Wei Reitman, Michael E. Huang, Yongkang Wang, Xiaoyu Li, Lei Deng, HanFei Shi, Song-Hai Poskanzer, Kira E. Lyons, David A. Nimmerjahn, Axel Ahrens, Misha B. Yu, Guoqiang Bradley Department of Electrical and Computer Engineering Virginia Polytechnic Institute and State University Arlington 22203 VA United States Janelia Research Campus Howard Hughes Medical Institute Ashburn 20147 VA United States Department of Molecular and Cellular Biology Harvard University Cambridge 02138 MA United States Graduate Program in Neuroscience Harvard Medical School Boston 02115 MA United States Waitt Advanced Biophotonics Center The Salk Institute for Biological Studies La Jolla 92037 CA United States Department of Biochemistry & Biophysics University of California San Francisco San Francisco CA United States Neuroscience Graduate Program University of California San Francisco San Francisco CA United States Centre for Discovery Brain Sciences University of Edinburgh Edinburgh BioQuarter Edinburgh EH16 4SB United Kingdom Gatsby Computational Neuroscience Unit UCL London W1T 4JG United Kingdom Kavli Institute for Fundamental Neuroscience San Francisco CA United States Department of Automation Tsinghua University Beijing 100084 China IDG/McGovern Institute for Brain Research Tsinghua University Beijing 100084 China New Cornerstone Science Laboratory Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University Beijing 100084 China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Fudan University Shanghai 200032 China Beijing National Research Center for Information Science and Technology Beijing 100084 China

Optical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development of new or improved biosensors and microscopy technology. This creates major computational challenges to extract and quantify biologically meaningful spatiotemporal patterns embedded within complex and rich data sources, many of which cannot be captured with existing methods. Here, we introduce activity quantification and analysis (AQuA2), a fast, accurate, and versatile data analysis platform built upon advanced machine-learning techniques. It decomposes complex live-imaging-based datasets into elementary signaling events, allowing accurate and unbiased quantification of molecular activities and identification of consensus functional units. We demonstrate applications across a wide range of biosensors, cell types, organs, animal models, microscopy techniques, and imaging approaches. As exemplar findings, we show how AQuA2 identified drug-dependent interactions between neurons and astroglia, as well as distinct sensorimotor signal propagation patterns in the mouse spinal cord. © 2025 The Author(s)

关键词： AQuA2 astrocytes cell interaction analysis functional units glial cells image analysis machine learning molecular spatiotemporal signals neurons time-lapse imaging

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Superior Performance of ZnGaO Solar-Blind Photodetectors by Implementing TFT Structure and Tunable ZNO Cycle Ratio

SSRN

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SSRN 2024年

作者： Fan, Hui-Chen Wang, Chen Xu, Yi-Hong Fan, Teng-Min Huang, Pao-Hsun Ruan, Yu-Jiao Wu, Tingzhu Kuo, Hao-Chung Wuu, Dong-Sing Lai, Feng-Min Lien, Shui-Yang Xiamen Key Laboratory of Development and Application for Advanced Semiconductor Coating Technology School of Opto-Electronic and Communication Engineering Xiamen University of Technology Xiamen361024 China School of Ocean Information Engineering Jimei University Jimei District Fujian Xiamen361021 China National Measurement and Testing Center for Flat Panel Display Industry Xiamen Institute of Measurement and Testing Xiamen361024 China National Integrated Circuit Industry and Education Integration Innovation Platform Department of Electronic Science Xiamen University Xiamen361005 China Department of Photonics Graduate Institute of Electro-Optical Engineering College of Electrical and Computer Engineering National Yang Ming Chiao Tung University Hsinchu30010 Taiwan Department of Applied Materials and Optoelectronic Engineering National Chi Nan University Nantou54561 Taiwan Department of Biomedical Engineering Da-Yeh University Changhua51591 Taiwan

In this study, plasma enhanced atomic layer deposition was used to prepare ZnGaO thin films with different ZnO cycle ratios from 0% to 50%, which were employed to fabricate the MSM-type and TFT-type solar-blind photodetector. The properties of the films and the performance of the solar blind photodetector are greatly affected by the ZnO cycle ratio. Appropriate Zn doping content decreases the ratio of oxygen vacancies and Zn interstitials in Ga2O3, while excessive Zn doping degrades the quality of the film. Compared to MSM-type photodetector, an obviously improved performance of ZnGaO TFT-type photodetector has been observed due to its self-amplified photocurrent and the reduced dark current controlled by gate voltage. At a ZnO cycle ratio of 40%, a superior performance of TFT-type solar-blind photodetector with an ultra-low dark current ~4.5×10-13 A, an excellent light switching ratio ~2.2×107, and an outstandingly high sensitivity ~34.31 A/W has been obtained. These results demonstrate that the incorporation of Zn dopants can effectively modulate the performance of Ga2O3 TFT-type photodetector providing a great perspective for cost-effective and high-performance solar-blind PDs. © 2024, The Authors. All rights reserved.

关键词： Zinc oxide

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Electrochemical biosensor based on an atomic layered composite of graphene oxide/graphene as an electrode material towards selective and sensitive detection of miRNA-21

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Microchemical Journal 2024年 199卷

作者： Huang, Min-Shin Govindasamy, Mani Chinnapaiyan, Sathishkumar Lin, Yi-Ting Lu, Shao-Yang Samukawa, Seiji Huang, Chi-Hsien Department of Materials Engineering Ming Chi University of Technology New Taipei City 243303 Taiwan International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City 24303 Taiwan Centre for Applied Research Saveetha School of Engineering Saveetha Institute of Medical and Technical Sciences (SIMATS) Chennai-602105 Tamil Nadu India Institute of Fluid Science Tohoku University Sendai 980-8577 Japan College of Electrical and Computer Engineering National Yang Ming Chiao Tung University Hsinchu 300093 Taiwan Division of Rheumatology Allergy and Immunology Chang Gung Memorial Hospital Taoyuan City 33305 Taiwan College of Engineering Chang Gung University Taoyuan City 33302 Taiwan

Development of an efficient technique towards the detection of miRNAs is highly significant for the timely diagnosis and prognosis of cancers. In this study, we utilized the chemical vapor deposition (CVD) technique to grow bilayer graphene (BLG) on copper foil and subsequently transferred the BLG to fluorine doped tin oxide (FTO) substrate via a facile wet transfer technique. The upper layer of the BLG was modified to graphene oxide (GO) with a low damage plasma treatment (LDPT) process to serve as a biomolecule receiving layer and the lower graphene layer (G) serves as an electron transport layer. The developed GO/G/FTO platform offers superior sensing ability towards the miRNA-21. The results demonstrated that the proposed GO/G/FTO substrate detect the miRNA-21 with a wide linear range (10 fM ∼ 1 nM), low limit of detection (3.18 fM), high sensitivity (0.6 mApM⁻¹cm⁻²), selectivity and stability via the differential pulse voltammetry method. Additionally, the sensors can efficiently discriminate the target miRNA-21 from its complementary base mismatched counterparts. The proposed approach serves as an excellent tool for the early diagnosis of diseases. © 2024 Elsevier B.V.

关键词： Atomic layer oxidation Biosensor Cancer biomarkers Electrochemical Graphene oxide Plasma treatment

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Surface morphology engineering of Cu for nanoscale strain control in graphene

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Surfaces and Interfaces 2025年 67卷

作者： Dong Jin Kim Cheolho Jeon Bo Hyeon Kim Jooyoung Yoon Seungryul Yoo Hwanuk Guim Yun Sung Woo Byung Hee Hong Joonhee Moon Program in Nano Science and Technology Graduate School of Convergence Science and Technology Seoul National University AbsSeoul 08826 Republic of Korea Graphene Square Inc. Suwon 16229 Republic of Korea Research Center for Materials Analysis Korea Basic Science Institute Daejeon 34133 Republic of Korea Department of Materials Science and Engineering Dankook University Chungnam 3116 Republic of Korea Institute of Plasma Technology Korea Institute of Fusion Energy (KFE) Gunsan Jeollabuk-do 54004 South Korea Department of Chemistry Seoul National University Seoul 08826 Republic of Korea

The most promising method for synthesizing high-quality, large-scale graphene films involves chemical vapor deposition (CVD) of carbon-containing precursors onto Cu substrates. During graphene growth in a CVD system, the interaction between graphene and the Cu substrate leads to the formation of anisotropic Cu step bunches, driven by interfacial surface energy minimization and the release of compressive stress during thermal cooling. It is widely acknowledged that a smooth substrate is crucial for achieving high-quality graphene, as graphene strain and Cu surface roughening induce wrinkles when transferred onto a silicon wafer, which negatively impacts the quality. Here, we introduce a straightforward approach for controlling strain in graphene by engineering the Cu surface morphology through mechanical tension during the growth process. We achieve a uniform distribution of low compressive strain across the graphene layer by applying varying mechanical weights to the Cu foil. Using atomic force microscopy (AFM), scanning electron microscopy (SEM), and Raman spectroscopy, we demonstrate that mechanical tension significantly reduces Cu surface roughness, providing a smoother interface for graphene growth. This work provides insights into the relationship between Cu surface structure and graphene strain, contributing to the optimization of substrate preparation for graphene synthesis and other related surface engineering applications.

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Unravelling the asphericities in the explosion and multi-faceted circumstellar matter of SN 2023ixf

arXiv

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arXiv 2024年

作者： Singh, Avinash Teja, Rishabh Singh Moriya, Takashi J. Maeda, Keiichi Kawabata, Koji S. Tanaka, Masaomi Imazawa, Ryo Nakaoka, Tatsuya Gangopadhyay, Anjasha Yamanaka, Masayuki Swain, Vishwajeet Sahu, D.K. Anupama, G.C. Kumar, Brajesh Anche, Ramya M. Sano, Yasuo Raj, A. Agnihotri, V.K. Bhalerao, Varun Bisht, D. Bisht, M.S. Belwal, K. Chakrabarti, S.K. Fujii, Mitsugu Nagayama, Takahiro Matsumoto, Katsura Hamada, Taisei Kawabata, Miho Kumar, Amit Kumar, Ravi Malkan, Brian K. Smith, Paul Sakagami, Yuta Taguchi, Kenta Tominaga, Nozomu Watanabe, Arata Hiroshima Astrophysical Science Centre Hiroshima University 1-3-1 Kagamiyama Higashi-Hiroshima Hiroshima739-8526 Japan Department of Astronomy The Oskar Klein Center Stockholm University AlbaNova University Center StockholmSE 106 91 Sweden Indian Institute of Astrophysics II Block Koramangala Karnataka Bengaluru560034 India Pondicherry University UT of Puducherry R.V. Nagar Kalapet Pondicherry605014 India National Astronomical Observatory of Japan National Institutes of Natural Sciences 2-21-1 Osawa Mitaka Tokyo181-8588 Japan Graduate Institute for Advanced Studies SOKENDAI 2-21-1 Osawa Mitaka Tokyo181-8588 Japan School of Physics and Astronomy Monash University ClaytonVIC3800 Australia Department of Astronomy Kyoto University Kitashirakawa-Oiwake-cho Sakyo-ku Kyoto606-8502 Japan Department of Physics Graduate School of Advanced Science and Engineering Hiroshima University 1-3-1 Kagamiyama Higashi-Hiroshima Hiroshima739-8526 Japan Astronomical Institute Tohoku University Aoba Sendai980-8578 Japan Department of Physics Graduate School of Advanced Science and Engineering Hiroshima Astrophysical Science Centre Hiroshima University 1-3-1 Kagamiyama Higashi-Hiroshima Hiroshima739-8526 Japan Graduate School of Science and Engineering Kagoshima University 1-21-35 Korimoto Kagoshima Kagoshima890-0065 Japan Department of Physics Indian Institute of Technology Bombay Powai Mumbai400076 India South-Western Institute for Astronomy Research Yunnan University Yunnan Kunming650504 China Steward Observatory University of Arizona 933N Cherry Avenue TucsonAZ85721 United States Observation and Data Center for Cosmosciences Faculty of Science Hokkaido University Kita-ku Sapporo-shi Hokkaido060-0810 Japan Nayoro Observatory 157-1 Nisshin Nayoro-shi Hokkaido096-0066 Japan Indian Centre for Space Physics 466 Barakhola Netai Nagar West Bengal Kolkata700099 India Cepheid Observatory India Fujii Kurosaki Observatory 4500 Kurosaki

We present a detailed investigation of photometric, spectroscopic, and polarimetric observations of the Type II SN 2023ixf. Earlier studies have provided compelling evidence for a delayed shock breakout from a confined dense circumstellar matter (CSM) enveloping the progenitor star. The temporal evolution of polarization in SN 2023ixf revealed three distinct peaks in polarization evolution at 1.4 d, 6.4 d, and 79.2 d, indicating an asymmetric dense CSM, an aspherical shock front and clumpiness in the low-density extended CSM, and an aspherical inner ejecta/He-core. SN 2023ixf displayed two dominant axes, one along the CSM-outer ejecta and the other along the inner ejecta/He-core, showcasing the independent origin of asymmetry in the early and late evolution. The argument for an aspherical shock front is further strengthened by the presence of a high-velocity broad absorption feature in the blue wing of the Balmer features in addition to the P-Cygni absorption post 16 d. Hydrodynamical light curve modeling indicated a progenitor mass of 10 M☉ with a radius of 470 R☉ and explosion energy of 2 × 1051 erg, along with 0.06 M☉ of 56 Ni, though these properties are not unique due to modeling degeneracies. The modeling also indicated a two-zone CSM: a confined dense CSM extending up to 5×1014 cm, with a mass-loss rate of 10−2 M☉ yr−1 and an extended CSM spanning from 5×1014 cm to at least 1016 cm with a mass-loss rate of 10−4 M☉ yr−1, both assuming a wind-velocity of 10 km s−1. The early nebular phase observations display an axisymmetric line profile of [O I], red-ward attenuation of the emission of Hα post 125 days and flattening in the Ks-band marking the onset of dust formation. Copyright © 2024, The Authors. All rights reserved.

关键词： Supernovae

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Cold atmospheric plasma-enabled platelet vesicle incorporated iron oxide nano-propellers for thrombolysis

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Materials Today Bio 2023年 23卷 100876页

作者： Jheng, Pei-Ru Chiang, Chia-Che Kang, Jiunn-Horng Fan, Yu-Jui Wu, Kevin C.-W. Chen, Yan-Ting Liang, Jia-Wei Bolouki, Nima Lee, Jyh-Wei Hsieh, Jang-Hsing Chuang, Er-Yuan Graduate Institute of Nanomedicine and Medical Engineering Graduate Institute of Biomedical Materials and Tissue Engineering Institute of Biomedical Optomechatronics International Ph.D. Program in Biomedical Engineering School of Biomedical Engineering College of Biomedical Engineering Professional Master Program in Artificial Intelligence in Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Department of Physical Medicine and Rehabilitation Taipei Medical University Hospital Taipei Taiwan Institute of Biomedical Engineering & Nanomedicine National Health Research Institute Keyan Road Zhunan Miaoli City350 Taiwan Department of Chemical Engineering National Taiwan University No.1 Sec. 4 Roosevelt Rd Taipei10617 Taiwan Department of Plasma Physics and Technology Faculty of Science Masaryk University Brno Czech Republic Center for Plasma and Thin Film Technologies Ming Chi University of Technology New Taipei City Taiwan Department of Materials Engineering Ming Chi University of Technology New Taipei City Taiwan Cell Physiology and Molecular Image Research Center Taipei Medical University-Wan Fang Hospital Taipei11696 Taiwan

A new approach to treating vascular blockages has been developed to overcome the limitations of current thrombolytic therapies. This approach involves biosafety and multimodal plasma-derived theranostic platelet vesicle incorporating iron oxide constructed nano-propellers platformed technology that possesses fluorescent and magnetic features and manifold thrombus targeting modes. The platform is capable of being guided and visualized remotely to specifically target thrombi, and it can be activated using near-infrared phototherapy along with an actuated magnet for magnetotherapy. In a murine model of thrombus lesion, this proposed multimodal approach showed an approximately 80 % reduction in thrombus residues. Moreover, the new strategy not only improves thrombolysis but also boosts the rate of lysis, making it a promising candidate for time-sensitive thrombolytic therapy. © 2023 The Authors

关键词： Infrared devices

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Magnetically Tuned Continuous Transition from Weak to Strong Coupling in Terahertz Magnon Polaritons

arXiv

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arXiv 2022年

作者： Baydin, Andrey Hayashida, Kenji Makihara, Takuma Tay, Fuyang Ma, Xiaoxuan Ren, Wei Ma, Guohong Noe, G. Timothy Katayama, Ikufumi Takeda, Jun Nojiri, Hiroyuki Cao, Shixun Bamba, Motoaki Kono, Junichiro Department of Electrical and Computer Engineering Rice University HoustonTX77005 United States The Smalley-Curl Institute Rice University HoustonTX77005 United States Division of Applied Physics Graduate School of Engineering Hokkaido University Hokkaido Sapporo060-8628 Japan Department of Physics and Astronomy Rice University HoustonTX77005 United States Applied Physics Graduate Program Smalley-Curl Institute Rice University HoustonTX77005 United States Department of Physics International Center of Quantum and Molecular Structures Materials Genome Institute Shanghai University Shanghai200444 China Department of Physics Graduate School of Engineering Science Yokohama National University Yokohama240-8501 Japan Institute for Materials Research Tohoku University Sendai980-8577 Japan The Hakubi Center for Advanced Research Kyoto University Kyoto606-8502 Japan Department of Physics I Kyoto University Kyoto606-8502 Japan PRESTO Japan Science and Technology Agency Kawaguchi332-0012 Japan Department of Materials Science and NanoEngineering Rice University HoustonTX77005 United States

Depending on the relative rates of coupling and dissipation, a light-matter coupled system is either in the weak- or strong-coupling regime. Here, we present a unique system where the coupling rate continuously increases with an externally applied magnetic field while the dissipation rate remains constant, allowing us to monitor a weak-to-strong coupling transition as a function of magnetic field. We observed a Rabi splitting of a terahertz magnon mode in yttrium orthoferrite above a threshold magnetic field of ∼14 T. Based on a microscopic theoretical model, we show that with increasing magnetic field the magnons transition into magnon polaritons through an exceptional point, which will open up new opportunities for in situ control of non-Hermitian systems. Copyright © 2022, The Authors. All rights reserved.

关键词： Polariton

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Titania Nanosheets Generates Peroxynitrite for S-Nitrosylation and Enhanced p53 Function in Lung Cancer Cells

Research Square

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Research Square 2021年

作者： Soonnarong, Rapeepun Tungsukruthai, Sucharat Nutho, Bodee Rungrotmongkol, Thanyada Vinayanuwattikun, Chanida Maluangnont, Tosapol Chanvorachote, Pithi Interdisciplinary Program of Pharmacology Graduate School Chulalongkorn University Bangkok Thailand Cell-based Drug and Health Products Development Research Unit Chulalongkorn University Bangkok Thailand Departments of Pharmacology and Physiology Faculty of Pharmaceutical Sciences Bangkok Thailand Department of Pharmacology Faculty of Science Mahidol University Bangkok Thailand Biocatalyst and Environmental Biotechnology Reseach Unit Department of Biochemistry Faculty of Science Chulalongkorn University Bangkok Thailand Program in Bioinformatics and Computational Biology Graduate School Chulalongkorn University Bangkok Thailand Division of Medical Oncology Department of Medicine Chulalongkorn University Bangkok Thailand College of Materials Innovation and Technology King Mongkut’s Institute of Technology Ladkrabang Bangkok Thailand

Background: Metal oxide nanomaterials are increasingly being exploited in cancer therapy thanks to their unique properties, which can enhance the efficacy of current cancer therapies. However, the nanotoxicity and mechanism of Ti0.8O2 nanosheets for specific site-targeting strategies in NSCLC have not yet been investigated. Methods: The effects of Ti0.8O2 nanosheets on cytotoxicity in NSCLC cells and normal cells were examined. The apoptosis characteristics, including condensed and fragmented nuclei, as assessed by positive staining with annexin V. The cellular uptake of the nanosheets and the induction of stress fiber were assessed via transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses, respectively. We also evaluated the expression of protein in death mechanism to identify the molecular mechanisms behind the toxicity of these cells. We investigated the relationship between S-nitrosylation and the increase in p53 stability by molecular dynamics. Results: Ti0.8O2 nanosheets caused cytotoxicity in several lung cancer cells, but not in normal cells. The nanosheets could enter lung cancer cells and exert an apoptosis induction. Results for protein analysis further indicated the activation of p53, increased Bax, decreased Bcl-2 and Mcl-1, and activation of caspase-3. The nanosheets also exhibited a substantial apoptosis effect in drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than that of cisplatin and etoposide. In terms of their mechanism of action, we found that the mode of apoptosis induction was through the generation of cellular ONOO− mediated the S-nitrosylation of p53 at C182. Molecular dynamics analysis further showed that the S-nitrosylation of one C182 stabilized the p53 dimer. Consequently, this nitrosylation of the protein led to an upregulation of p53 through its stabilization. Conclusions: Taking all the evidence together, we provided info

关键词： Molecular dynamics

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In silico identification of a novel Cdc2-like kinase 2 (CLK2) inhibitor in triple negative breast cancer

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Protein science 2024年第6期33卷 e5004-e5004页

作者： Huang, Cheng-Chiao Hsu, Chia-Ming Chao, Min-Wu Hsu, Kai-Cheng Lin, Tony Eight Yen, Shih-Chung Tu, Huang-Ju Pan, Shiow-Lin Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei Taiwan Division of General Surgery Department of Surgery Taipei Medical University Hospital Taipei Taiwan Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan School of Medicine College of Medicine National Sun Yat-sen University Kaohsiung Taiwan Institute of Biopharmaceutical Sciences College of Medicine National Sun Yat-sen University Kaohsiung Taiwan The Doctoral Program of Clinical and Experimental Medicine College of Medicine National Sun Yat-sen University Kaohsiung Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taipei Taiwan TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei Taiwan TMU Research Center of Drug Discovery Taipei Medical University Taipei Taiwan Warshel Institute for Computational Biology The Chinese University of Hong Kong (Shenzhen) Guangdong Shenzhen China

Dysregulation of RNA splicing processes is intricately linked to tumorigenesis in various cancers, especially breast cancer. Cdc2-like kinase 2 (CLK2), an oncogenic RNA-splicing kinase pivotal in breast cancer, plays a significant role, particularly in the context of triple-negative breast cancer (TNBC), a subtype marked by substantial medical challenges due to its low survival rates. In this study, we employed a structure-based virtual screening (SBVS) method to identify potential CLK2 inhibitors with novel chemical structures for treating TNBC. Compound 670551 emerged as a novel CLK2 inhibitor with a 50% inhibitory concentration (IC₅₀) value of 619.7 nM. Importantly, Compound 670551 exhibited high selectivity for CLK2 over other protein kinases. Functionally, this compound significantly reduced the survival and proliferation of TNBC cells. Results from a cell-based assay demonstrated that this inhibitor led to a decrease in RNA splicing proteins, such as SRSF4 and SRSF6, resulting in cell apoptosis. In summary, we identified a novel CLK2 inhibitor as a promising potential treatment for TNBC therapy. © 2024 The Authors. Protein science published by Wiley Periodicals LLC on behalf of The Protein Society.

关键词： CLK2 drug discovery kinase inhibitor structure-based virtual screening triple-negative breast cancer

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