ACS Publications. Most Trusted. Most Cited. Most Read
My Activity

Leucettines, a Class of Potent Inhibitors of cdc2-Like Kinases and Dual Specificity, Tyrosine Phosphorylation Regulated Kinases Derived from the Marine Sponge Leucettamine B: Modulation of Alternative Pre-RNA Splicing

View Author Information
Université de Rennes 1, Sciences Chimiques de Rennes, UMR CNRS 6226, Groupe ‘Ingénierie Chimique & Molécules pour le Vivant’ (ICMV), Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes cedex, France
Nuffield Department of Clinical Medicine, Structural Genomics Consortium, Oxford University, Old Road Campus Research Building, Headington, Oxford OX3 7DQ, U.K.
§ Station Biologique de Roscoff, CNRS, ‘Protein Phosphorylation and Human Disease’ Group, Place G. Teissier, BP 74, 29682 Roscoff, France
Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
# Charité-Universitätsmedizin-Berlin, Campus B. Franklin, Centrum für Herz- und Kreislaufmedizin, Hindenburgdamm 30, 12203 Berlin, Germany
(L.M. (biology)) Tel: +33.(0) Fax: +33.5(0) E-mail: [email protected]. (F.C. (chemistry)) E-mail: [email protected]. Tel: +33.(0) Fax: 33.(0) (J.P.B. (chemistry)) Tel: +33.(0) Fax: 33.(0) E-mail: [email protected]
Cite this: J. Med. Chem. 2011, 54, 12, 4172–4186
Publication Date (Web):May 26, 2011
Copyright © 2011 American Chemical Society

    Article Views





    Other access options
    Supporting Info (1)»


    Abstract Image

    We here report on the synthesis, optimization, and biological characterization of leucettines, a family of kinase inhibitors derived from the marine sponge leucettamine B. Stepwise synthesis of analogues starting from the natural structure, guided by activity testing on eight purified kinases, led to highly potent inhibitors of CLKs and DYRKs, two families of kinases involved in alternative pre-mRNA splicing and Alzheimer’s disease/Down syndrome. Leucettine L41 was cocrystallized with CLK3. It interacts with key residues located within the ATP-binding pocket of the kinase. Leucettine L41 inhibits the phosphorylation of serine/arginine-rich proteins (SRp), a family of proteins regulating pre-RNA splicing. Indeed leucettine L41 was demonstrated to modulate alternative pre-mRNA splicing, in a cell-based reporting system. Leucettines should be further explored as pharmacological tools to study and modulate pre-RNA splicing. Leucettines may also be investigated as potential therapeutic drugs in Alzheimer’s disease (AD) and in diseases involving abnormal pre-mRNA splicing.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.


    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Supporting Information

    Jump To

    General experimental methods and characterization data (1H and 13C NMR, HRMS, and elemental analysis) for all compounds. This material is available free of charge via the Internet at

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system:

    Cited By

    This article is cited by 120 publications.

    1. Muhammad Naufal, Elvira Hermawati, Yana Maolana Syah, Ace Tatang Hidayat, Ika Wiani Hidayat, Jamaludin Al-Anshori. Structure–Activity Relationship Study and Design Strategies of Hydantoin, Thiazolidinedione, and Rhodanine-Based Kinase Inhibitors: A Two-Decade Review. ACS Omega 2024, 9 (4) , 4186-4209.
    2. Mattias F. Lindberg, Emmanuel Deau, Frédéric Miege, Marie Greverie, Didier Roche, Nicolas George, Pascal George, Laura Merlet, Julie Gavard, Sander J. T. Brugman, Edwin Aret, Paul Tinnemans, René de Gelder, Jan Sadownik, Eva Verhofstad, Dennis Sleegers, Sara Santangelo, Julien Dairou, Álvaro Fernandez-Blanco, Mara Dierssen, Andreas Krämer, Stefan Knapp, Laurent Meijer. Chemical, Biochemical, Cellular, and Physiological Characterization of Leucettinib-21, a Down Syndrome and Alzheimer’s Disease Drug Candidate. Journal of Medicinal Chemistry 2023, 66 (23) , 15648-15670.
    3. Emmanuel Deau, Mattias F. Lindberg, Frédéric Miege, Didier Roche, Nicolas George, Pascal George, Andreas Krämer, Stefan Knapp, Laurent Meijer. Leucettinibs, a Class of DYRK/CLK Kinase Inhibitors Inspired by the Marine Sponge Natural Product Leucettamine B. Journal of Medicinal Chemistry 2023, 66 (15) , 10694-10714.
    4. Mattias F. Lindberg, Emmanuel Deau, Jonas Arfwedson, Nicolas George, Pascal George, Patricia Alfonso, Ana Corrionero, Laurent Meijer. Comparative Efficacy and Selectivity of Pharmacological Inhibitors of DYRK and CLK Protein Kinases. Journal of Medicinal Chemistry 2023, 66 (6) , 4106-4130.
    5. Tania Tahtouh, Emilie Durieu, Benoît Villiers, Céline Bruyère, Thu Lan Nguyen, Xavier Fant, Kwang H. Ahn, Leepakshi Khurana, Emmanuel Deau, Mattias F. Lindberg, Elodie Sévère, Frédéric Miege, Didier Roche, Emmanuelle Limanton, Jean-Martial L’Helgoual’ch, Guillaume Burgy, Solène Guiheneuf, Yann Herault, Debra A. Kendall, François Carreaux, Jean-Pierre Bazureau, Laurent Meijer. Structure–Activity Relationship in the Leucettine Family of Kinase Inhibitors. Journal of Medicinal Chemistry 2022, 65 (2) , 1396-1417.
    6. Kunal Kumar, Chalada Suebsuwong, Peng Wang, Adolfo Garcia-Ocana, Andrew F. Stewart, Robert J. DeVita. DYRK1A Inhibitors as Potential Therapeutics for β-Cell Regeneration for Diabetes. Journal of Medicinal Chemistry 2021, 64 (6) , 2901-2922.
    7. Dnyandev B. Jarhad, Karishma K. Mashelkar, Hong-Rae Kim, Minsoo Noh, Lak Shin Jeong. Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) Inhibitors as Potential Therapeutics. Journal of Medicinal Chemistry 2018, 61 (22) , 9791-9810.
    8. Sirilak Wangngae, Mookda Pattarawarapan, and Wong Phakhodee . Ph3P/I2-Mediated Synthesis of N,N′,N″-Substituted Guanidines and 2-Iminoimidazolin-4-ones from Aryl Isothiocyanates. The Journal of Organic Chemistry 2017, 82 (19) , 10331-10340.
    9. Qi-Zheng Sun, Gui-Feng Lin, Lin-Li Li, Xi-Ting Jin, Lu-Yi Huang, Guo Zhang, Wei Yang, Kai Chen, Rong Xiang, Chong Chen, Yu-Quan Wei, Guang-Wen Lu, and Sheng-Yong Yang . Discovery of Potent and Selective Inhibitors of Cdc2-Like Kinase 1 (CLK1) as a New Class of Autophagy Inducers. Journal of Medicinal Chemistry 2017, 60 (14) , 6337-6352.
    10. Qingqing Zhou, Athena F. Phoa, Ramzi H. Abbassi, Monira Hoque, Tristan A. Reekie, Josep S. Font, Renae M. Ryan, Brett W. Stringer, Bryan W. Day, Terrance G. Johns, Lenka Munoz, and Michael Kassiou . Structural Optimization and Pharmacological Evaluation of Inhibitors Targeting Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases (DYRK) and CDC-like kinases (CLK) in Glioblastoma. Journal of Medicinal Chemistry 2017, 60 (5) , 2052-2070.
    11. Kenji Ohe and Masatoshi Hagiwara . Modulation of Alternative Splicing with Chemical Compounds in New Therapeutics for Human Diseases. ACS Chemical Biology 2015, 10 (4) , 914-924.
    12. Hannes Falke, Apirat Chaikuad, Anja Becker, Nadège Loaëc, Olivier Lozach, Samira Abu Jhaisha, Walter Becker, Peter G. Jones, Lutz Preu, Knut Baumann, Stefan Knapp, Laurent Meijer, and Conrad Kunick . 10-Iodo-11H-indolo[3,2-c]quinoline-6-carboxylic Acids Are Selective Inhibitors of DYRK1A. Journal of Medicinal Chemistry 2015, 58 (7) , 3131-3143.
    13. Mehdi A. Beniddir, Erell Le Borgne, Bogdan I. Iorga, Nadège Loaëc, Olivier Lozach, Laurent Meijer, Khalijah Awang, and Marc Litaudon . Acridone Alkaloids from Glycosmis chlorosperma as DYRK1A Inhibitors. Journal of Natural Products 2014, 77 (5) , 1117-1122.
    14. Stéphanie Gourdain, Julien Dairou, Clément Denhez, Linh Chi Bui, Fernando Rodrigues-Lima, Nathalie Janel, Jean M. Delabar, Kevin Cariou, and Robert H. Dodd . Development of DANDYs, New 3,5-Diaryl-7-azaindoles Demonstrating Potent DYRK1A Kinase Inhibitory Activity. Journal of Medicinal Chemistry 2013, 56 (23) , 9569-9585.
    15. Julie A. Spicer, Gersande Lena, Dani M. Lyons, Kristiina M. Huttunen, Christian K. Miller, Patrick D. O’Connor, Matthew Bull, Nuala Helsby, Stephen M. F. Jamieson, William A. Denny, Annette Ciccone, Kylie A. Browne, Jamie A. Lopez, Jesse Rudd-Schmidt, Ilia Voskoboinik, and Joseph A. Trapani . Exploration of a Series of 5-Arylidene-2-thioxoimidazolidin-4-ones as Inhibitors of the Cytolytic Protein Perforin. Journal of Medicinal Chemistry 2013, 56 (23) , 9542-9555.
    16. Sandip B. Bharate, Sanghapal D. Sawant, Parvinder Pal Singh, and Ram A. Vishwakarma . Kinase Inhibitors of Marine Origin. Chemical Reviews 2013, 113 (8) , 6761-6815.
    17. Yongmei Pan, Yanli Wang, and Stephen H. Bryant . Pharmacophore and 3D-QSAR Characterization of 6-Arylquinazolin-4-amines as Cdc2-like Kinase 4 (Clk4) and Dual Specificity Tyrosine-phosphorylation-regulated Kinase 1A (Dyrk1A) Inhibitors. Journal of Chemical Information and Modeling 2013, 53 (4) , 938-947.
    18. Vassilios Myrianthopoulos, Marina Kritsanida, Nicolas Gaboriaud-Kolar, Prokopios Magiatis, Yoan Ferandin, Emilie Durieu, Olivier Lozach, Daniel Cappel, Meera Soundararajan, Panagis Filippakopoulos, Woody Sherman, Stefan Knapp, Laurent Meijer, Emmanuel Mikros, and Alexios-Leandros Skaltsounis . Novel Inverse Binding Mode of Indirubin Derivatives Yields Improved Selectivity for DYRK Kinases. ACS Medicinal Chemistry Letters 2013, 4 (1) , 22-26.
    19. Rajâa Boulahjar, Aziz Ouach, Chiurato Matteo, Stephane Bourg, Myriam Ravache, Rémy le Guével, Séverine Marionneau, Thibauld Oullier, Olivier Lozach, Laurent Meijer, Christiane Guguen-Guillouzo, Saïd Lazar, Mohamed Akssira, Yves Troin, Gérald Guillaumet, and Sylvain Routier . Novel Tetrahydropyrido[1,2-a]isoindolone Derivatives (Valmerins): Potent Cyclin-Dependent Kinase/Glycogen Synthase Kinase 3 Inhibitors with Antiproliferative Activities and Antitumor Effects in Human Tumor Xenografts. Journal of Medicinal Chemistry 2012, 55 (22) , 9589-9606.
    20. Tania Tahtouh, Jonathan M. Elkins, Panagis Filippakopoulos, Meera Soundararajan, Guillaume Burgy, Emilie Durieu, Claude Cochet, Ralf S. Schmid, Donald C. Lo, Florent Delhommel, Anselm E. Oberholzer, Laurence H. Pearl, François Carreaux, Jean-Pierre Bazureau, Stefan Knapp, and Laurent Meijer . Selectivity, Cocrystal Structures, and Neuroprotective Properties of Leucettines, a Family of Protein Kinase Inhibitors Derived from the Marine Sponge Alkaloid Leucettamine B. Journal of Medicinal Chemistry 2012, 55 (21) , 9312-9330.
    21. Yueying Yang, Huiru Xie, Xinbo Yu, Yang Liu, Hui Wang, Hua Li, Lixia Chen. Design, synthesis and evaluation of the first DYRK1A degraders for promoting the proliferation of pancreatic β-cells. Chinese Chemical Letters 2024, 172 , 109570.
    22. Mengqiu Song, Luping Pang, Mengmeng Zhang, Yingzi Qu, Kyle Vaughn Laster, Zigang Dong. Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases. Signal Transduction and Targeted Therapy 2023, 8 (1)
    23. Roderick C. Slieker, Louise A. Donnelly, Elina Akalestou, Livia Lopez-Noriega, Rana Melhem, Ayşim Güneş, Frederic Abou Azar, Alexander Efanov, Eleni Georgiadou, Hermine Muniangi-Muhitu, Mahsa Sheikh, Giuseppe N. Giordano, Mikael Åkerlund, Emma Ahlqvist, Ashfaq Ali, Karina Banasik, Søren Brunak, Marko Barovic, Gerard A. Bouland, Frédéric Burdet, Mickaël Canouil, Iulian Dragan, Petra J. M. Elders, Celine Fernandez, Andreas Festa, Hugo Fitipaldi, Phillippe Froguel, Valborg Gudmundsdottir, Vilmundur Gudnason, Mathias J. Gerl, Amber A. van der Heijden, Lori L. Jennings, Michael K. Hansen, Min Kim, Isabelle Leclerc, Christian Klose, Dmitry Kuznetsov, Dina Mansour Aly, Florence Mehl, Diana Marek, Olle Melander, Anne Niknejad, Filip Ottosson, Imre Pavo, Kevin Duffin, Samreen K. Syed, Janice L. Shaw, Over Cabrera, Timothy J. Pullen, Kai Simons, Michele Solimena, Tommi Suvitaival, Asger Wretlind, Peter Rossing, Valeriya Lyssenko, Cristina Legido Quigley, Leif Groop, Bernard Thorens, Paul W. Franks, Gareth E. Lim, Jennifer Estall, Mark Ibberson, Joline W. J. Beulens, Leen M ’t Hart, Ewan R. Pearson, Guy A. Rutter. Identification of biomarkers for glycaemic deterioration in type 2 diabetes. Nature Communications 2023, 14 (1)
    24. Subha Dahal, Kiera Clayton, Tyler Cabral, Ran Cheng, Shahrzad Jahanshahi, Choudhary Ahmed, Amrit Koirala, Alonso Villasmil Ocando, Ramy Malty, Terek Been, Javier Hernandez, Maria Mangos, David Shen, Mohan Babu, John Calarco, Benoit Chabot, Liliana Attisano, Walid A. Houry, Alan Cochrane, . On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine. Journal of Virology 2023, 97 (10)
    25. Pau Nadal Rodríguez, Ouldouz Ghashghaei, Anna M. Schoepf, Sam Benson, Marc Vendrell, Rodolfo Lavilla. Charting the Chemical Reaction Space around a Multicomponent Combination: Controlled Access to a Diverse Set of Biologically Relevant Scaffolds. Angewandte Chemie 2023, 135 (41)
    26. Pau Nadal Rodríguez, Ouldouz Ghashghaei, Anna M. Schoepf, Sam Benson, Marc Vendrell, Rodolfo Lavilla. Charting the Chemical Reaction Space around a Multicomponent Combination: Controlled Access to a Diverse Set of Biologically Relevant Scaffolds. Angewandte Chemie International Edition 2023, 62 (41)
    27. Yuping Yang, Xiaoxiao Fan, Yongjian Liu, Danyang Ye, Cen Liu, Hongliu Yang, Zhijun Su, Yuanyuan Zhang, Yonggang Liu. Function and inhibition of DYRK1A: Emerging roles of treating multiple human diseases. Biochemical Pharmacology 2023, 212 , 115521.
    28. Barbara Pucelik, Agata Barzowska, Anna Czarna, . DYRK1A inhibitors leucettines and TGF-β inhibitor additively stimulate insulin production in beta cells, organoids, and isolated mouse islets. PLOS ONE 2023, 18 (5) , e0285208.
    29. Ahmed K. ElHady, Dalia S. El‐Gamil, Ashraf H. Abadi, Mohammad Abdel‐Halim, Matthias Engel. An overview of cdc2‐like kinase 1 (Clk1) inhibitors and their therapeutic indications. Medicinal Research Reviews 2023, 43 (2) , 343-398.
    30. Tao Yang, Yingxue Yang, Yong Chen, Minghai Tang, Mingsong Shi, Yang Tian, Xue Yuan, Zhuang Yang, Lijuan Chen. Rational design and appraisal of selective Cdc2-Like kinase 1 (Clk1) inhibitors as novel autophagy inducers for the treatment of acute liver injury (ALI). European Journal of Medicinal Chemistry 2023, 250 , 115168.
    31. Sukanya, Bhupendra G. Prajapati, Vaishali M. Patil, Bhanwar Singh Choudhary. Dual Specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) Inhibitors: The Quest for a Disease-Modifying Treatment for Alzheimer’s Disease. 2023, 69-94.
    32. Amedeo Vetere, Vishal S. Parekh, Ashley E. Modell, Veronika M. Shoba, Amit Choudhary, Bridget K. Wagner. Chemical Approaches for Beta-cell Biology. 2022, 1-52.
    33. Teresa Gianferrara, Eleonora Cescon, Ilenia Grieco, Giampiero Spalluto, Stephanie Federico. Glycogen Synthase Kinase 3β Involvement in Neuroinflammation and Neurodegenerative Diseases. Current Medicinal Chemistry 2022, 29 (27) , 4631-4697.
    34. Tong Liu, Yuxi Wang, Jiaxing Wang, Changyu Ren, Hao Chen, Jifa Zhang. DYRK1A inhibitors for disease therapy: Current status and perspectives. European Journal of Medicinal Chemistry 2022, 229 , 114062.
    35. Yasmeen T. AlNajjar, Moustafa Gabr, Ahmed K. ElHady, Mohamed Salah, Gerrit Wilms, Ashraf H. Abadi, Walter Becker, Mohammad Abdel-Halim, Matthias Engel. Discovery of novel 6-hydroxybenzothiazole urea derivatives as dual Dyrk1A/α-synuclein aggregation inhibitors with neuroprotective effects. European Journal of Medicinal Chemistry 2022, 227 , 113911.
    36. Helin Atas-Ozcan, Véronique Brault, Arnaud Duchon, Yann Herault. Dyrk1a from Gene Function in Development and Physiology to Dosage Correction across Life Span in Down Syndrome. Genes 2021, 12 (11) , 1833.
    37. Khadidja Bourahla, Solène Guihéneuf, Emmanuelle Limanton, Ludovic Paquin, Rémy Le Guével, Thierry Charlier, Mustapha Rahmouni, Emilie Durieu, Olivier Lozach, François Carreaux, Laurent Meijer, Jean-Pierre Bazureau. Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A. Pharmaceuticals 2021, 14 (11) , 1086.
    38. Mohamed H. Elsherbeny, Ahmed Elkamhawy, Hossam Nada, Magda H. Abdellattif, Kyeong Lee, Eun Joo Roh. Development of New Meridianin/Leucettine-Derived Hybrid Small Molecules as Nanomolar Multi-Kinase Inhibitors with Antitumor Activity. Biomedicines 2021, 9 (9) , 1131.
    39. Stefania Demuro, Rita M. C. Di Martino, Jose A. Ortega, Andrea Cavalli. GSK-3β, FYN, and DYRK1A: Master Regulators in Neurodegenerative Pathways. International Journal of Molecular Sciences 2021, 22 (16) , 9098.
    40. Salar Hafez Ghoran, Anake Kijjoa. Marine-Derived Compounds with Anti-Alzheimer’s Disease Activities. Marine Drugs 2021, 19 (8) , 410.
    41. Samar Bou Zeid, Aline Hamade, Fadia Najjar, Francois Carreaux, Samar Eid. Microwave-assisted synthesis of new 2-aryl and 2-alkylimidazolones and evaluation of their in vitro anticancer activity and their in vivo toxicity on zebrafish embryos. Chemical Papers 2021, 75 (6) , 2549-2560.
    42. Ariadna Recasens, Sean J. Humphrey, Michael Ellis, Monira Hoque, Ramzi H. Abbassi, Brianna Chen, Mitchell Longworth, Elise J. Needham, David E. James, Terrance G. Johns, Bryan W. Day, Michael Kassiou, Pengyi Yang, Lenka Munoz. Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells. Cell Death Discovery 2021, 7 (1)
    43. Mattias F. Lindberg, Laurent Meijer. Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview. International Journal of Molecular Sciences 2021, 22 (11) , 6047.
    44. Vasudha Tandon, Laureano de la Vega, Sourav Banerjee. Emerging roles of DYRK2 in cancer. Journal of Biological Chemistry 2021, 296 , 100233.
    45. Alzahraa A.M. Fergany, Victor V. Tatarskiy. RNA Splicing: Basic Aspects Underlie Antitumor Targeting. Recent Patents on Anti-Cancer Drug Discovery 2020, 15 (4) , 293-305.
    46. Xuanyi Li, Yinqiu Xu, Hequan Yao, Kejiang Lin. Chemical space exploration based on recurrent neural networks: applications in discovering kinase inhibitors. Journal of Cheminformatics 2020, 12 (1)
    47. Cláudia Bessa, Paulo Matos, Peter Jordan, Vânia Gonçalves. Alternative Splicing: Expanding the Landscape of Cancer Biomarkers and Therapeutics. International Journal of Molecular Sciences 2020, 21 (23) , 9032.
    48. Katarina L. Keel, Jetze J. Tepe. The preparation of (4 H )-imidazol-4-ones and their application in the total synthesis of natural products. Organic Chemistry Frontiers 2020, 7 (20) , 3284-3311.
    49. Ming-Hua Hsu, Cheng-Ying Hsieh, Mohit Kapoor, Jui-Hsun Chang, Hsueh-Liang Chu, Tsai-Mu Cheng, Kai-Cheng Hsu, Tony Eight Lin, Fu-Yuan Tsai, Jia-Cherng Horng. Leucettamine B analogs and their carborane derivative as potential anti-cancer agents: Design, synthesis, and biological evaluation. Bioorganic Chemistry 2020, 98 , 103729.
    50. Courtney Ackeifi, Ethan Swartz, Kunal Kumar, Hongtao Liu, Suebsuwong Chalada, Esra Karakose, Donald K. Scott, Adolfo Garcia-Ocaña, Roberto Sanchez, Robert J. DeVita, Andrew F. Stewart, Peng Wang. Pharmacologic and genetic approaches define human pancreatic β cell mitogenic targets of DYRK1A inhibitors. JCI Insight 2020, 5 (1)
    51. 勇 王. The Dual-Specificity Tyrosine Phosphorylation Regulated Kinase 1A and the Advances of Its Inhibitors. Hans Journal of Medicinal Chemistry 2020, 08 (02) , 38-50.
    52. Benoît Souchet, Mickael Audrain, Jean Marie Billard, Julien Dairou, Romain Fol, Nicola Salvatore Orefice, Satoru Tada, Yuchen Gu, Gaelle Dufayet-Chaffaud, Emmanuelle Limanton, François Carreaux, Jean-Pierre Bazureau, Sandro Alves, Laurent Meijer, Nathalie Janel, Jérôme Braudeau, Nathalie Cartier. Inhibition of DYRK1A proteolysis modifies its kinase specificity and rescues Alzheimer phenotype in APP/PS1 mice. Acta Neuropathologica Communications 2019, 7 (1)
    53. A.J. Black, J.R. Gamarra, J. Giudice. More than a messenger: Alternative splicing as a therapeutic target. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 2019, 1862 (11-12) , 194395.
    54. Christian Lechner, Maren Flaßhoff, Hannes Falke, Lutz Preu, Nadége Loaëc, Laurent Meijer, Stefan Knapp, Apirat Chaikuad, Conrad Kunick. [b]-Annulated Halogen-Substituted Indoles as Potential DYRK1A Inhibitors. Molecules 2019, 24 (22) , 4090.
    55. Richard Rubenstein, Deep R. Sharma, Binggong Chang, Nassima Oumata, Morgane Cam, Lise Vaucelle, Mattias F. Lindberg, Allen Chiu, Thomas Wisniewski, Kevin K. W. Wang, Laurent Meijer. Novel Mouse Tauopathy Model for Repetitive Mild Traumatic Brain Injury: Evaluation of Long-Term Effects on Cognition and Biomarker Levels After Therapeutic Inhibition of Tau Phosphorylation. Frontiers in Neurology 2019, 10
    56. Riyo Maruki Imamura, Kazuo Kumagai, Hirofumi Nakano, Takayoshi Okabe, Tetsuo Nagano, Hirotatsu Kojima. Inexpensive High-Throughput Screening of Kinase Inhibitors Using One-Step Enzyme-Coupled Fluorescence Assay for ADP Detection. SLAS Discovery 2019, 24 (3) , 284-294.
    57. Maria L. Arbones, Aurore Thomazeau, Akiko Nakano-Kobayashi, Masatoshi Hagiwara, Jean M. Delabar. DYRK1A and cognition: A lifelong relationship. Pharmacology & Therapeutics 2019, 194 , 199-221.
    58. Jacqueline Olender, Norman H. Lee. Role of Alternative Splicing in Prostate Cancer Aggressiveness and Drug Resistance in African Americans. 2019, 119-139.
    59. Ankita Pathak, Ankit Rohilla, Tanya Gupta, Md Jawaid Akhtar, Md Rafi Haider, Kalicharan Sharma, Kashif Haider, M. Shahar Yar. DYRK1A kinase inhibition with emphasis on neurodegeneration: A comprehensive evolution story-cum-perspective. European Journal of Medicinal Chemistry 2018, 158 , 559-592.
    60. Sarah S. Darwish, Mohammad Abdel-Halim, Mohamed Salah, Ashraf H. Abadi, Walter Becker, Matthias Engel. Development of novel 2,4-bispyridyl thiophene–based compounds as highly potent and selective Dyrk1A inhibitors. Part I: Benzamide and benzylamide derivatives. European Journal of Medicinal Chemistry 2018, 157 , 1031-1050.
    61. Rosanna Meine, Walter Becker, Hannes Falke, Lutz Preu, Nadège Loaëc, Laurent Meijer, Conrad Kunick. Indole-3-Carbonitriles as DYRK1A Inhibitors by Fragment-Based Drug Design. Molecules 2018, 23 (2) , 64.
    62. Mange Ram Yadav, Mahesh A. Barmade, Rupesh V. Chikhale, Prashant R. Murumkar. Computational Modelling of Kinase Inhibitors as Anti-Alzheimer Agents. 2018, 347-417.
    63. Thu Lan Nguyen, Arnaud Duchon, Antigoni Manousopoulou, Nadège Loaëc, Benoît Villiers, Guillaume Pani, Meltem Karatas, Anna E. Mechling, Laura-Adela Harsan, Emmanuelle Limanton, Jean-Pierre Bazureau, François Carreaux, Spiros D. Garbis, Laurent Meijer, Yann Herault. Correction of cognitive deficits in mouse models of Down syndrome by a pharmacological inhibitor of DYRK1A. Disease Models & Mechanisms 2018, 84
    64. Thu Lan Nguyen, Corinne Fruit, Yann Hérault, Laurent Meijer, Thierry Besson. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors: a survey of recent patent literature. Expert Opinion on Therapeutic Patents 2017, 27 (11) , 1183-1199.
    65. Nadège Loaëc, Eletta Attanasio, Benoît Villiers, Emilie Durieu, Tania Tahtouh, Morgane Cam, Rohan Davis, Aline Alencar, Mélanie Roué, Marie-Lise Bourguet-Kondracki, Peter Proksch, Emmanuelle Limanton, Solène Guiheneuf, François Carreaux, Jean-Pierre Bazureau, Michelle Klautau, Laurent Meijer. Marine-Derived 2-Aminoimidazolone Alkaloids. Leucettamine B-Related Polyandrocarpamines Inhibit Mammalian and Protozoan DYRK & CLK Kinases. Marine Drugs 2017, 15 (10) , 316.
    66. Tonko Dražić, Marin Roje. β-Lactam rearrangements into five-membered heterocycles. Chemistry of Heterocyclic Compounds 2017, 53 (9) , 953-962.
    67. Ahalya Balachandran, Alan Cochrane. Screening for small molecule inhibitors of HIV-1 Gag expression. Methods 2017, 126 , 201-208.
    68. Simon J. Shaw, Dane A. Goff, Nan Lin, Rajinder Singh, Wei Li, John McLaughlin, Kristen A. Baltgalvis, Donald G. Payan, Todd M. Kinsella. Developing DYRK inhibitors derived from the meridianins as a means of increasing levels of NFAT in the nucleus. Bioorganic & Medicinal Chemistry Letters 2017, 27 (11) , 2617-2621.
    69. Tonko Dražić, Krešimir Molčanov, Mladenka Jurin, Marin Roje. Synthesis of marine alkaloids leucettamines B and C by β-lactam ring rearrangement. Synthetic Communications 2017, 47 (8) , 764-770.
    70. Anne Walter, Apirat Chaikuad, Nadège Loaëc, Lutz Preu, Stefan Knapp, Laurent Meijer, Conrad Kunick, Oliver Koch. Identification of CLK1 Inhibitors by a Fragment–linking Based Virtual Screening. Molecular Informatics 2017, 36 (4)
    71. Lyamin Z. Bendjeddou, Nadège Loaëc, Benoît Villiers, Eric Prina, Gerald F. Späth, Hervé Galons, Laurent Meijer, Nassima Oumata. Exploration of the imidazo[1,2-b]pyridazine scaffold as a protein kinase inhibitor. European Journal of Medicinal Chemistry 2017, 125 , 696-709.
    72. David O. Bates, Jonathan C. Morris, Sebastian Oltean, Lucy F. Donaldson, . Pharmacology of Modulators of Alternative Splicing. Pharmacological Reviews 2017, 69 (1) , 63-79.
    73. Christelle N’ta Ambeu, Camille Déliko Dago, Wacothon Karime Coulibaly, Yves-Alain Békro, Janat A. Mamyrbekova-Békro, Béatrice Foll-Josselin, Audrey Defontaine, Claire Delehouzé, Stéphane Bach, Sandrine Ruchaud, Rémy Le Guével, Anne Corlu, Philippe Jéhan, Fabian Lambert, Nicolas Le Yondre, Jean-Pierre Bazureau. Microwave synthesis of new 3-(3-aminopropyl)-5-arylidene- 2-thioxo-1,3-thiazolidine-4-ones as potential Ser/Thr protein kinase inhibitors. Medicinal Chemistry Research 2016, 25 (12) , 2940-2958.
    74. Marie Lawson, Jordi Rodrigo, Blandine Baratte, Thomas Robert, Claire Delehouzé, Olivier Lozach, Sandrine Ruchaud, Stéphane Bach, Jean-Daniel Brion, Mouad Alami, Abdallah Hamze. Synthesis, biological evaluation and molecular modeling studies of imidazo[1,2- a ]pyridines derivatives as protein kinase inhibitors. European Journal of Medicinal Chemistry 2016, 123 , 105-114.
    75. Masahiko Ajiro, Shuang Tang, John Doorbar, Zhi-Ming Zheng, . Serine/Arginine-Rich Splicing Factor 3 and Heterogeneous Nuclear Ribonucleoprotein A1 Regulate Alternative RNA Splicing and Gene Expression of Human Papillomavirus 18 through Two Functionally Distinguishable cis Elements. Journal of Virology 2016, 90 (20) , 9138-9152.
    76. Akanksha Kulshreshtha, Poonam Piplani. Current pharmacotherapy and putative disease-modifying therapy for Alzheimer’s disease. Neurological Sciences 2016, 37 (9) , 1403-1435.
    77. Marica Mariano, Rolf W. Hartmann, Matthias Engel. Systematic diversification of benzylidene heterocycles yields novel inhibitor scaffolds selective for Dyrk1A, Clk1 and CK2. European Journal of Medicinal Chemistry 2016, 112 , 209-216.
    78. Silvia Stotani, Fabrizio Giordanetto, Federico Medda. DYRK1A inhibition as potential treatment for Alzheimer’s disease. Future Medicinal Chemistry 2016, 8 (6) , 681-696.
    79. Hyeongki Kim, Kyu-Sun Lee, Ae-Kyeong Kim, Miri Choi, Kwangman Choi, Mingu Kang, Seung-Wook Chi, Min-Sung Lee, Jeong-Soo Lee, So-Young Lee, Woo-Joo Song, Kweon Yu, Sungchan cho. A chemical with proven clinical safety restores Down syndrome-related phenotypes via DYRK1A inhibition. Disease Models & Mechanisms 2016, 507
    80. Christian Muchardt. Transcriptional activity of endogenous retroviruses in multiple sclerosis: a sign of deficient chromatin-mediated silencing. Epigenomics 2015, 7 (8) , 1235-1237.
    81. Qifang Xu, Kimberly L. Malecka, Lauren Fink, E. Joseph Jordan, Erin Duffy, Samuel Kolander, Jeffrey R. Peterson, Roland L. Dunbrack. Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases. Science Signaling 2015, 8 (405)
    82. Gaëlle Naert, Valentine Ferré, Johann Meunier, Emeline Keller, Susanna Malmström, Laurent Givalois, François Carreaux, Jean-Pierre Bazureau, Tangui Maurice. Leucettine L41, a DYRK1A-preferential DYRKs/CLKs inhibitor, prevents memory impairments and neurotoxicity induced by oligomeric Aβ25–35 peptide administration in mice. European Neuropsychopharmacology 2015, 25 (11) , 2170-2182.
    83. Diaa T.A. Youssef, Gamal A. Mohamed, Lamiaa A. Shaala, Jihan M. Badr, Faida H. Bamanie, Sabrin R.M. Ibrahim. New purine alkaloids from the Red Sea marine tunicate Symplegma rubra. Phytochemistry Letters 2015, 13 , 212-217.
    84. Ulrike Leppert, Andreas Eisenreich. The role of tissue factor isoforms in cancer biology. International Journal of Cancer 2015, 137 (3) , 497-503.
    85. Rammohan R. Yadav, Sadhana Sharma, Prashant Joshi, Abubakar Wani, Ram A. Vishwakarma, Ajay Kumar, Sandip B. Bharate. Meridianin derivatives as potent Dyrk1A inhibitors and neuroprotective agents. Bioorganic & Medicinal Chemistry Letters 2015, 25 (15) , 2948-2952.
    86. Yue Chi, Ling Xu, Shanshan Du, Haihan Yan, Wen‐Xiong Zhang, Zhenfeng Xi. Synthesis and Mechanistic Study of Cyclic Oxoguanidines via Zn(OTf) 2 ‐Catalyzed Guanylation/Amidation from Readily Available Amino Acid Esters and Carbodiimides. Chemistry – A European Journal 2015, 21 (29) , 10369-10378.
    87. Ramzi Abbassi, Terrance G. Johns, Michael Kassiou, Lenka Munoz. DYRK1A in neurodegeneration and cancer: Molecular basis and clinical implications. Pharmacology & Therapeutics 2015, 151 , 87-98.
    88. Camille Dago, Christelle Ambeu, Wacothon-Karime Coulibaly, Yves-Alain Békro, Janat Mamyrbékova, Audrey Defontaine, Blandine Baratte, Stéphane Bach, Sandrine Ruchaud, Rémy Guével, Myriam Ravache, Anne Corlu, Jean-Pierre Bazureau. Synthetic Development of New 3-(4-Arylmethylamino)butyl-5-arylidene-rhodanines under Microwave Irradiation and Their Effects on Tumor Cell Lines and against Protein Kinases. Molecules 2015, 20 (7) , 12412-12435.
    89. Elodie Brun, Abdelmounaim Safer, François Carreaux, Khadidja Bourahla, Jean-Martial L'helgoua'ch, Jean-Pierre Bazureau, Jose Villalgordo. Microwave-Assisted Condensation Reactions of Acetophenone Derivatives and Activated Methylene Compounds with Aldehydes Catalyzed by Boric Acid under Solvent-Free Conditions. Molecules 2015, 20 (6) , 11617-11631.
    90. Séverine Coutadeur, Hélène Benyamine, Laurence Delalonde, Catherine de Oliveira, Bertrand Leblond, Alicia Foucourt, Thierry Besson, Anne‐Sophie Casagrande, Thierry Taverne, Angélique Girard, Matthew P. Pando, Laurent Désiré. A novel DYRK1A (Dual specificity tyrosine phosphorylation‐regulated kinase 1A) inhibitor for the treatment of Alzheimer's disease: effect on Tau and amyloid pathologies in vitro. Journal of Neurochemistry 2015, 133 (3) , 440-451.
    91. Rémy Hemelaere, François Carreaux, Bertrand Carboni. A Diastereoselective Route to trans ‐2‐Aryl‐2,3‐dihydrobenzofurans through Sequential Cross‐Metathesis/Isomerization/Allylboration Reactions: Synthesis of Bioactive Neolignans. European Journal of Organic Chemistry 2015, 2015 (11) , 2470-2481.
    92. Wacothon Karime Coulibaly, Ludovic Paquin, Anoubilé Bénie, Yves-Alain Békro, Rémy Le Guével, Myriam Ravache, Anne Corlu, Jean Pierre Bazureau. Prospective study directed to the synthesis of unsymmetrical linked bis-5-arylidene rhodanine derivatives via “one-pot two steps” reactions under microwave irradiation with their antitumor activity. Medicinal Chemistry Research 2015, 24 (4) , 1653-1661.
    93. Ulli Rothweiler, Jonas Eriksson, Wenche Stensen, Frederick Leeson, Richard A. Engh, John S. Svendsen. Luciferin and derivatives as a DYRK selective scaffold for the design of protein kinase inhibitors. European Journal of Medicinal Chemistry 2015, 94 , 140-148.
    94. C Delehouzé, K Godl, N Loaëc, C Bruyère, N Desban, N Oumata, H Galons, T I Roumeliotis, E G Giannopoulou, J Grenet, D Twitchell, J Lahti, N Mouchet, M-D Galibert, S D Garbis, L Meijer. CDK/CK1 inhibitors roscovitine and CR8 downregulate amplified MYCN in neuroblastoma cells. Oncogene 2014, 33 (50) , 5675-5687.
    95. Alicia Foucourt, Damien Hédou, Carole Dubouilh-Benard, Angélique Girard, Thierry Taverne, Anne-Sophie Casagrande, Laurent Désiré, Bertrand Leblond, Thierry Besson. Design and Synthesis of Thiazolo[5,4-f]quinazolines as DYRK1A Inhibitors, Part II. Molecules 2014, 19 (10) , 15411-15439.
    96. Alicia Foucourt, Damien Hédou, Carole Dubouilh-Benard, Laurent Désiré, Anne-Sophie Casagrande, Bertrand Leblond, Nadège Loäec, Laurent Meijer, Thierry Besson. Design and Synthesis of Thiazolo[5,4-f]quinazolines as DYRK1A Inhibitors, Part I. Molecules 2014, 19 (10) , 15546-15571.
    97. Sandrine Houzé, Nha-Thu Hoang, Olivier Lozach, Jacques Le Bras, Laurent Meijer, Hervé Galons, Luc Demange. Several Human Cyclin-Dependent Kinase Inhibitors, Structurally Related to Roscovitine, As New Anti-Malarial Agents. Molecules 2014, 19 (9) , 15237-15257.
    98. James A. DeCaprio, Anette Duensing. The DREAM complex in antitumor activity of imatinib mesylate in gastrointestinal stromal tumors. Current Opinion in Oncology 2014, 26 (4) , 415-421.
    99. Suk Min Jang, Saliha Azebi, Guillaume Soubigou, Christian Muchardt. DYRK1A phoshorylates histone H3 to differentially regulate the binding of HP1 isoforms and antagonize HP1‐mediated transcriptional repression. EMBO reports 2014, 15 (6) , 686-694.
    100. Solene Guiheneuf, Ludovic Paquin, François Carreaux, Emilie Durieu, Thierry Roisnel, Laurent Meijer, Jean-Pierre Bazureau. New 5-ylidene rhodanine derivatives based on the dispacamide A model. Molecular Diversity 2014, 18 (2) , 375-388.
    Load all citations

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Your Mendeley pairing has expired. Please reconnect