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

Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease

View Author Information
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via P. Giuria 9, 10125 Torino, Italy
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy
§ Faculty of Biology, Medicine and Health, The University of Manchester, R4.004 AV Hill Building, Oxford Road, Manchester, U.K.
Molecular Inflammation Group, Biomedical Research Institute of Murcia (IMIB-Arrixaca), University Clinical Hospital “Virgen de la Arrixaca”, University of Murcia, Carretera Buenavista s/n, 30120, El Palmar, Murcia, Spain
Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia
# Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy
*P.P.: e-mail, [email protected]; phone, +34 868885038.
*M.B.: e-mail, [email protected]; phone, +39 011 6707667.
Cite this: J. Med. Chem. 2017, 60, 9, 3656–3671
Publication Date (Web):April 14, 2017
https://doi.org/10.1021/acs.jmedchem.6b01624
Copyright © 2017 American Chemical Society

    Article Views

    4254

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options
    Supporting Info (2)»

    Abstract

    Abstract Image

    Pharmacological inhibition of NLRP3 inflammasome activation may offer a new option in the treatment of inflammatory bowel disease. In this work, we report the design, synthesis, and biological screening of a series of acrylate derivatives as NLRP3 inhibitors. The in vitro determination of reactivity, cytotoxicity, NLRP3 ATPase inhibition, and antipyroptotic properties allowed the selection of 11 (INF39), a nontoxic, irreversible NLRP3 inhibitor able to decrease interleukin-1β release from macrophages. Bioluminescence resonance energy transfer experiments proved that this compound was able to directly interfere with NLRP3 activation in cells. In vivo studies confirmed the ability of the selected lead to alleviate the effects of colitis induced by 2,4-dinitrobenzenesulfonic acid in rats after oral administration.

    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.

    Recommended

    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

    ARTICLE SECTIONS
    Jump To

    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jmedchem.6b01624.

    • Structures of NLRP3 pathway inhibitors studied in IBD models and relevant references, reactivity of 11 with cysteamine, stability of 11 in human serum, BRET assay approach, table of criteria used for scoring of colonic macroscopic damage, and damage-score determination in 11-treated animals (PDF)

    • Molecular formula strings (CSV)

    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: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 127 publications.

    1. Na Li, Ruijia Zhang, Minghai Tang, Min Zhao, Xueqin Jiang, Xiaoying Cai, Neng Ye, Kaiyue Su, Jing Peng, Xinlu Zhang, Wenshuang Wu, Haoyu Ye. Recent Progress and Prospects of Small Molecules for NLRP3 Inflammasome Inhibition. Journal of Medicinal Chemistry 2023, 66 (21) , 14447-14473. https://doi.org/10.1021/acs.jmedchem.3c01370
    2. Na Li, Xueqin Jiang, Ruijia Zhang, Neng Ye, Minghai Tang, Xiaoying Cai, Kaiyue Su, Jing Peng, Xinlu Zhang, Min Zhao, Wenshuang Wu, Haoyu Ye. Discovery of Triazinone Derivatives as Novel, Specific, and Direct NLRP3 Inflammasome Inhibitors for the Treatment of DSS-Induced Ulcerative Colitis. Journal of Medicinal Chemistry 2023, 66 (19) , 13428-13451. https://doi.org/10.1021/acs.jmedchem.3c00696
    3. Xinyi Wu, Ping Sun, Xiuhui Chen, Lei Hua, Haowei Cai, Zhuorong Liu, Cheng Zhang, Shuli Liang, Yanhong Chen, Dan Wu, Yitao Ou, Wenhui Hu, Zhongjin Yang. Discovery of a Novel Oral Proteasome Inhibitor to Block NLRP3 Inflammasome Activation with Anti-inflammation Activity. Journal of Medicinal Chemistry 2022, 65 (18) , 11985-12001. https://doi.org/10.1021/acs.jmedchem.2c00523
    4. Yaoyao Yan, Chen Xing, Yun Xiao, Xiaobao Shen, Zhaoyan Zhang, Chuanbiao He, Jing-Bo Shi, Mingming Liu, Xinhua Liu. Discovery and Anti-Inflammatory Activity Evaluation of a Novel CDK8 Inhibitor through Upregulation of IL-10 for the Treatment of Inflammatory Bowel Disease In Vivo. Journal of Medicinal Chemistry 2022, 65 (10) , 7334-7362. https://doi.org/10.1021/acs.jmedchem.2c00356
    5. Ruijia Zhang, Feng Hong, Min Zhao, Xiaoying Cai, Xueqin Jiang, Neng Ye, Kaiyue Su, Na Li, Minghai Tang, Xu Ma, Hengfan Ni, Lun Wang, Li Wan, Lijuan Chen, Wenshuang Wu, Haoyu Ye. New Highly Potent NLRP3 Inhibitors: Furanochalcone Velutone F Analogues. ACS Medicinal Chemistry Letters 2022, 13 (4) , 560-569. https://doi.org/10.1021/acsmedchemlett.1c00597
    6. Xujun Cao, Anthony F. Cordova, Lingyin Li. Therapeutic Interventions Targeting Innate Immune Receptors: A Balancing Act. Chemical Reviews 2022, 122 (3) , 3414-3458. https://doi.org/10.1021/acs.chemrev.1c00716
    7. Liu Zeng Chen, Xing Xing Zhang, Ming Ming Liu, Jing Wu, Duo Ma, Liang Zhuo Diao, Qingshan Li, Yan Shuang Huang, Rui Zhang, Ban Feng Ruan, Xin Hua Liu. Discovery of Novel Pterostilbene-Based Derivatives as Potent and Orally Active NLRP3 Inflammasome Inhibitors with Inflammatory Activity for Colitis. Journal of Medicinal Chemistry 2021, 64 (18) , 13633-13657. https://doi.org/10.1021/acs.jmedchem.1c01007
    8. Mohd Abdullaha, Mehboob Ali, Dilpreet Kour, Ramesh Mudududdla, Parul Khajuria, Ajay Kumar, Sandip B. Bharate. Tetramethoxystilbene Inhibits NLRP3 Inflammasome Assembly via Blocking the Oligomerization of Apoptosis-Associated Speck-like Protein Containing Caspase Recruitment Domain: In Vitro and In Vivo Evaluation. ACS Pharmacology & Translational Science 2021, 4 (4) , 1437-1448. https://doi.org/10.1021/acsptsci.1c00126
    9. Zhen Dai, Xiao-yi Chen, Lu-yan An, Cui-cui Li, Ni Zhao, Fan Yang, Song-tao You, Chen-zhi Hou, Kan Li, Cheng Jiang, Qi-dong You, Bin Di, Li-li Xu. Development of Novel Tetrahydroquinoline Inhibitors of NLRP3 Inflammasome for Potential Treatment of DSS-Induced Mouse Colitis. Journal of Medicinal Chemistry 2021, 64 (1) , 871-889. https://doi.org/10.1021/acs.jmedchem.0c01924
    10. Yuqi Jiang, Liu He, Jakob Green, Hallie Blevins, Chunqing Guo, Sulay Harsiddhbhai Patel, Matthew S. Halquist, MaryPeace McRae, Jürgen Venitz, Xiang-Yang Wang, Shijun Zhang. Discovery of Second-Generation NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization. Journal of Medicinal Chemistry 2019, 62 (21) , 9718-9731. https://doi.org/10.1021/acs.jmedchem.9b01155
    11. Sumin Lee, Qianying Ye, Hyeyun Yang, Sojung Lee, YeJi Kim, Nahyun Lee, Darwin Gonzalez-Cox, Dong-Keun Yi, Soo-Yong Kim, Sangho Choi, Taesoo Choi, Man S. Kim, Seong Su Hong, Chun Whan Choi, Yoonsung Lee, Yong Hwan Park. Aiouea padiformis extract exhibits anti-inflammatory effects by inhibiting the ATPase activity of NLRP3. Scientific Reports 2024, 14 (1) https://doi.org/10.1038/s41598-024-55651-z
    12. Shengying Lou, Miaolian Wu, Sunliang Cui. Targeting NLRP3 Inflammasome: Structure, Function, and Inhibitors. Current Medicinal Chemistry 2024, 31 (15) , 2021-2051. https://doi.org/10.2174/0109298673289984231127062528
    13. Xiu Chen, Pingping Zhang, Yu Zhang, Mengzhu Wei, Tian Tian, Dacheng Zhu, Yanling Guan, Wei Wei, Yang Ma. The research progression of direct NLRP3 inhibitors to treat inflammatory disorders. Cellular Immunology 2024, 397-398 , 104810. https://doi.org/10.1016/j.cellimm.2024.104810
    14. Hao Chen, Hu Yue, Yuyun Yan, Nannan Wu, Dan Wu, Ping Sun, Wenhui Hu, Zhongjin Yang. Design, synthesis and biological evaluation of tanshinone IIA derivatives as NLRP3 inflammasome inhibitors. Bioorganic & Medicinal Chemistry Letters 2024, 55 , 129725. https://doi.org/10.1016/j.bmcl.2024.129725
    15. Nenghua Zhou, Yun Zhang, Yan Jiao, Jinshan Nan, Anjie Xia, Bo Mu, Guifeng Lin, Xun Li, Shanshan Zhang, Shengyong Yang, Linli Li. Discovery of a novel pyroptosis inhibitor acting though modulating glutathionylation to suppress NLRP3-related signal pathway. International Immunopharmacology 2024, 127 , 111314. https://doi.org/10.1016/j.intimp.2023.111314
    16. Valentina Arrè, Rosanna Scialpi, Matteo Centonze, Gianluigi Giannelli, Maria Principia Scavo, Roberto Negro. The ‘speck’-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis. Journal of Biomedical Science 2023, 30 (1) https://doi.org/10.1186/s12929-023-00983-7
    17. Lian Wang, Yanghui Zhu, Lu Zhang, Linghong Guo, Xiaoyun Wang, Zhaoping Pan, Xian Jiang, Fengbo Wu, Gu He. Mechanisms of PANoptosis and relevant small-molecule compounds for fighting diseases. Cell Death & Disease 2023, 14 (12) https://doi.org/10.1038/s41419-023-06370-2
    18. Jacqueline Cavalcante-Silva, Timothy J. Koh. Targeting the NOD-Like Receptor Pyrin Domain Containing 3 Inflammasome to Improve Healing of Diabetic Wounds. Advances in Wound Care 2023, 12 (11) , 644-656. https://doi.org/10.1089/wound.2021.0148
    19. Meibo Duan, Lei Sun, Xinzi He, Zechen Wang, Yunlei Hou, Yanfang Zhao. Medicinal chemistry strategies targeting NLRP3 inflammasome pathway: A recent update from 2019 to mid-2023. European Journal of Medicinal Chemistry 2023, 260 , 115750. https://doi.org/10.1016/j.ejmech.2023.115750
    20. Zihao Li, Senlin Ji, Chuyu Wu, Jiayong Wu, Runjing Cao, Yunshu Wang, Yun Xu, Jingwei Li, Cun-Jin Zhang. Identification of D359-0396 as a novel inhibitor of the activation of NLRP3 inflammasome. Neurochemistry International 2023, 169 , 105565. https://doi.org/10.1016/j.neuint.2023.105565
    21. Wendan Zhang, Honghong Jiang, Pengli Huang, Gaosong Wu, Qun Wang, Xin Luan, Hongwei Zhang, Dianping Yu, Hongru Wang, Dong Lu, Haonan Wang, Huazhang An, Sanhong Liu, Weidong Zhang. Dracorhodin targeting CMPK2 attenuates inflammation: A novel approach to sepsis therapy. Clinical and Translational Medicine 2023, 13 (10) https://doi.org/10.1002/ctm2.1449
    22. Xu Zheng, Dan Zhao, Ye Jin, Yang Liu, Da Liu. Role of the NLRP3 inflammasome in gynecological disease. Biomedicine & Pharmacotherapy 2023, 166 , 115393. https://doi.org/10.1016/j.biopha.2023.115393
    23. Ling Liao, Zhi-Peng Zhao, Bo-Ning Gu, Jin-Sheng Yu, Jian Zhou. Palladium-Catalyzed Hydroalkylation of Alkoxyallenes Using Monofluorinated Nucleophiles. Synthesis 2023, 55 (19) , 3090-3103. https://doi.org/10.1055/a-2096-6929
    24. Jian Zou, Rujie Yang, Ruibing Feng, Jiayue Liu, Jian-Bo Wan. Ginsenoside Rk2, a dehydroprotopanaxadiol saponin, alleviates alcoholic liver disease via regulating NLRP3 and NLRP6 inflammasome signaling pathways in mice. Journal of Pharmaceutical Analysis 2023, 13 (9) , 999-1012. https://doi.org/10.1016/j.jpha.2023.05.005
    25. Simone Gastaldi, Carmine Rocca, Eleonora Gianquinto, Maria Concetta Granieri, Valentina Boscaro, Federica Blua, Barbara Rolando, Elisabetta Marini, Margherita Gallicchio, Anna De Bartolo, Naomi Romeo, Rosa Mazza, Francesco Fedele, Pasquale Pagliaro, Claudia Penna, Francesca Spyrakis, Massimo Bertinaria, Tommaso Angelone. Discovery of a novel 1,3,4-oxadiazol-2-one-based NLRP3 inhibitor as a pharmacological agent to mitigate cardiac and metabolic complications in an experimental model of diet-induced metaflammation. European Journal of Medicinal Chemistry 2023, 257 , 115542. https://doi.org/10.1016/j.ejmech.2023.115542
    26. Miguel A. Ortega, Diego De Leon-Oliva, Cielo García-Montero, Oscar Fraile-Martinez, Diego Liviu Boaru, Amador Velazquez de Castro, Miguel A. Saez, Laura Lopez-Gonzalez, Julia Bujan, Miguel Angel Alvarez-Mon, Natalio García-Honduvilla, Raul Diaz-Pedrero, Melchor Alvarez-Mon. Reframing the link between metabolism and NLRP3 inflammasome: therapeutic opportunities. Frontiers in Immunology 2023, 14 https://doi.org/10.3389/fimmu.2023.1232629
    27. Elisabetta Ferrara, Ilaria Converti, Roberta Scarola, Francesco Carlo Tartaglia, Antonio Gnoni, Gaetano Isola, Biagio Rapone. Mechanism behind the Upregulation of Proteins Associated with the NLRP3 Inflammasome in Periodontitis and Their Role in the Immune Response in Diabetes—A Systematic Review. Applied Sciences 2023, 13 (14) , 8278. https://doi.org/10.3390/app13148278
    28. Qiang Ma, . Pharmacological Inhibition of the NLRP3 Inflammasome: Structure, Molecular Activation, and Inhibitor-NLRP3 Interaction. Pharmacological Reviews 2023, 75 (3) , 487-520. https://doi.org/10.1124/pharmrev.122.000629
    29. Daniela Maria Tanase, Emilia Valasciuc, Evelina Maria Gosav, Anca Ouatu, Oana Nicoleta Buliga-Finis, Mariana Floria, Minela Aida Maranduca, Ionela Lacramioara Serban. Portrayal of NLRP3 Inflammasome in Atherosclerosis: Current Knowledge and Therapeutic Targets. International Journal of Molecular Sciences 2023, 24 (9) , 8162. https://doi.org/10.3390/ijms24098162
    30. Jiexia Wen, Bin Xuan, Yang Liu, Liwei Wang, Li He, Xiangcai Meng, Tao Zhou, Yimin Wang. NLRP3 inflammasome-induced pyroptosis in digestive system tumors. Frontiers in Immunology 2023, 14 https://doi.org/10.3389/fimmu.2023.1074606
    31. Pritam Thapa, Sunil P. Upadhyay, Vikas Singh, Varun C. Boinpelly, Jianping Zhou, David K. Johnson, Prajwal Gurung, Eung Seok Lee, Ram Sharma, Mukut Sharma. Chalcone: A potential scaffold for NLRP3 inflammasome inhibitors. European Journal of Medicinal Chemistry Reports 2023, 7 , 100100. https://doi.org/10.1016/j.ejmcr.2022.100100
    32. Xiaolu Zhang, Ziyu Wang, Yujia Zheng, Qun Yu, Miao Zeng, Liding Bai, Lin Yang, Maojuan Guo, Xijuan Jiang, Jiali Gan. Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review). International Journal of Molecular Medicine 2023, 51 (4) https://doi.org/10.3892/ijmm.2023.5238
    33. Xiaoyan Zhan, Qiang Li, Guang Xu, Xiaohe Xiao, Zhaofang Bai. The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors. Frontiers in Immunology 2023, 13 https://doi.org/10.3389/fimmu.2022.1109938
    34. Petra Sušjan-Leite, Iva Hafner-Bratkovič. Assessing the ATP Binding Ability of NLRP3 from Cell Lysates by a Pull-down Assay. 2023, 257-267. https://doi.org/10.1007/978-1-0716-3350-2_17
    35. Rebecca E. Tweedell, Shelbi Christgen, Thirumala-Devi Kanneganti. Inflammasomes as integral components of PANoptosomes in the regulation of cell death. 2023, 525-538. https://doi.org/10.1016/B978-0-323-91802-2.00033-5
    36. Alexander Hooftman, Alessia Zotta, Luke A.J. O'Neill. Therapeutic opportunities targeting the NLRP3 inflammasome. 2023, 555-563. https://doi.org/10.1016/B978-0-323-91802-2.00035-9
    37. Massimo Bertinaria, Simone Gastaldi, Elisabetta Marini. Development of selective NLRP3 inflammasome inhibitors. 2023, 565-582. https://doi.org/10.1016/B978-0-323-91802-2.00037-2
    38. Lei Pang, Hongmei Liu, Hongyu Quan, Hehuan Sui, Yi Jia. Development of novel oridonin analogs as specifically targeted NLRP3 inflammasome inhibitors for the treatment of dextran sulfate sodium-induced colitis. European Journal of Medicinal Chemistry 2023, 245 , 114919. https://doi.org/10.1016/j.ejmech.2022.114919
    39. Shaoqiang Wei, Min Feng, Shidong Zhang. Molecular Characteristics of Cell Pyroptosis and Its Inhibitors: A Review of Activation, Regulation, and Inhibitors. International Journal of Molecular Sciences 2022, 23 (24) , 16115. https://doi.org/10.3390/ijms232416115
    40. Bao Hai, Tianli Mao, Chuanchao Du, Fei Jia, Yu Liu, Qingpeng Song, Xiaoyu Pan, Xiaoguang Liu, Bin Zhu. USP14 promotes pyroptosis of human annulus fibrosus cells derived from patients with intervertebral disc degeneration through deubiquitination of NLRP3. Acta Biochimica et Biophysica Sinica 2022, 54 (11) , 1720-1730. https://doi.org/10.3724/abbs.2022171
    41. Xiangna Zhang, Ana Xu, Yingying Ran, Chao Wei, Fei Xie, Jingde Wu. Design, synthesis and biological evaluation of phenyl vinyl sulfone based NLRP3 inflammasome inhibitors. Bioorganic Chemistry 2022, 128 , 106010. https://doi.org/10.1016/j.bioorg.2022.106010
    42. Linh Thi Nhat Nguyen, Huu Dat Nguyen, Yun Joong Kim, Tinh Thi Nguyen, Thuy Thi Lai, Yoon Kyoung Lee, Hyeo-il Ma, Young Eun Kim. Role of NLRP3 Inflammasome in Parkinson’s Disease and Therapeutic Considerations. Journal of Parkinson's Disease 2022, 12 (7) , 2117-2133. https://doi.org/10.3233/JPD-223290
    43. Meng Song, Zijun Chen, Ruian Qiu, Tingwei Zhi, Wenmin Xie, Yingya Zhou, Nachuan Luo, Fuqian Chen, Fang Liu, Chuangpeng Shen, Sheng Lin, Fengxue Zhang, Yong Gao, Changhui Liu. Inhibition of NLRP3-mediated crosstalk between hepatocytes and liver macrophages by geniposidic acid alleviates cholestatic liver inflammatory injury. Redox Biology 2022, 55 , 102404. https://doi.org/10.1016/j.redox.2022.102404
    44. Rebecca C. Coll, Kate Schroder, Pablo Pelegrín. NLRP3 and pyroptosis blockers for treating inflammatory diseases. Trends in Pharmacological Sciences 2022, 43 (8) , 653-668. https://doi.org/10.1016/j.tips.2022.04.003
    45. Yiming Xu, Yulong Xu, Hallie Blevins, Chunqing Guo, Savannah Biby, Xiang-Yang Wang, Changning Wang, Shijun Zhang. Development of sulfonamide-based NLRP3 inhibitors: Further modifications and optimization through structure-activity relationship studies. European Journal of Medicinal Chemistry 2022, 238 , 114468. https://doi.org/10.1016/j.ejmech.2022.114468
    46. Shigui Xue, Yan Xue, Danbo Dou, Huan Wu, Ping Zhang, Yang Gao, Yini Tang, Zehua Xia, Sen Yang, Sizhen Gu, . Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway. Disease Markers 2022, 2022 , 1-15. https://doi.org/10.1155/2022/2782112
    47. Chen Chen, Pinglong Xu. Activation and Pharmacological Regulation of Inflammasomes. Biomolecules 2022, 12 (7) , 1005. https://doi.org/10.3390/biom12071005
    48. Hallie M. Blevins, Yiming Xu, Savannah Biby, Shijun Zhang. The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases. Frontiers in Aging Neuroscience 2022, 14 https://doi.org/10.3389/fnagi.2022.879021
    49. Samo Roškar, Iva Hafner-Bratkovič. The Role of Inflammasomes in Osteoarthritis and Secondary Joint Degeneration Diseases. Life 2022, 12 (5) , 731. https://doi.org/10.3390/life12050731
    50. Federica Sodano, Claudia Cristiano, Barbara Rolando, Elisabetta Marini, Loretta Lazzarato, Mariarosaria Cuozzo, Stefania Albrizio, Roberto Russo, Maria Grazia Rimoli. Galactosylated Prodrugs: A Strategy to Improve the Profile of Nonsteroidal Anti-Inflammatory Drugs. Pharmaceuticals 2022, 15 (5) , 552. https://doi.org/10.3390/ph15050552
    51. Shelbi Christgen, Rebecca E. Tweedell, Thirumala-Devi Kanneganti. Programming inflammatory cell death for therapy. Pharmacology & Therapeutics 2022, 232 , 108010. https://doi.org/10.1016/j.pharmthera.2021.108010
    52. Yan Jiao, Jinshan Nan, Bo Mu, Yun Zhang, Nenghua Zhou, Shunhua Yang, Shanshan Zhang, Wanting Lin, Falu Wang, Anjie Xia, Zhixing Cao, Pei Chen, Zhiling Pan, Guifeng Lin, Shulei Pan, Huachao Bin, Linli Li, Shengyong Yang. Discovery of a novel and potent inhibitor with differential species-specific effects against NLRP3 and AIM2 inflammasome-dependent pyroptosis. European Journal of Medicinal Chemistry 2022, 232 , 114194. https://doi.org/10.1016/j.ejmech.2022.114194
    53. Alejandro Peñin-Franch, José Antonio García-Vidal, Carlos Manuel Martínez, Pilar Escolar-Reina, Rosa M Martínez-Ojeda, Ana I Gómez, Juan M Bueno, Francisco Minaya-Muñoz, Fermín Valera-Garrido, Francesc Medina-Mirapeix, Pablo Pelegrín. Galvanic current activates the NLRP3 inflammasome to promote Type I collagen production in tendon. eLife 2022, 11 https://doi.org/10.7554/eLife.73675
    54. Min-Ran Wang, Lan-Fang Huang, Cong Guo, Jing Yang, Shuai Dong, Jiang-Jiang Tang, Jin-Ming Gao. Identification of NLRP3 as a covalent target of 1,6-O,O-diacetylbritannilactone against neuroinflammation by quantitative thiol reactivity profiling (QTRP). Bioorganic Chemistry 2022, 119 , 105536. https://doi.org/10.1016/j.bioorg.2021.105536
    55. Christopher B. Ryder, Hannah C. Kondolf, Meghan E. O'Keefe, Bowen Zhou, Derek W. Abbott. Chemical Modulation of Gasdermin-Mediated Pyroptosis and Therapeutic Potential. Journal of Molecular Biology 2022, 434 (4) , 167183. https://doi.org/10.1016/j.jmb.2021.167183
    56. Haowen Zhang, Hanyu Chen, Xiang Wu, Tong Sun, Manlu Fan, Huaqin Tong, Yejin Zhu, Zhe Yin, Weixin Sun, Chao Zhang, Xiao Zheng, Xiaohu Chen. Tetramethylpyrazine alleviates diabetes-induced high platelet response and endothelial adhesion via inhibiting NLRP3 inflammasome activation. Phytomedicine 2022, 96 , 153860. https://doi.org/10.1016/j.phymed.2021.153860
    57. Yun Zhang, Yan Jiao, Xun Li, Sheng Gao, Nenghua Zhou, Jianan Duan, Meixia Zhang. Pyroptosis: A New Insight Into Eye Disease Therapy. Frontiers in Pharmacology 2021, 12 https://doi.org/10.3389/fphar.2021.797110
    58. Yi Li, Jianping Chen, Andrew A Bolinger, Haiying Chen, Zhiqing Liu, Yingzi Cong, Allan R Brasier, Irina V Pinchuk, Bing Tian, Jia Zhou. Target-Based Small Molecule Drug Discovery Towards Novel Therapeutics for Inflammatory Bowel Diseases. Inflammatory Bowel Diseases 2021, 27 (Supplement_2) , S38-S62. https://doi.org/10.1093/ibd/izab190
    59. Shuai Shao, Chengjuan Chen, Gaona Shi, Yu Zhou, Yazi Wei, Ningyu Fan, Yan Yang, Lei Wu, Tiantai Zhang. Therapeutic potential of the target on NLRP3 inflammasome in multiple sclerosis. Pharmacology & Therapeutics 2021, 227 , 107880. https://doi.org/10.1016/j.pharmthera.2021.107880
    60. Seongkeun Jeong, Changyu Kang, Sohee Park, Sanghyun Ju, Jin-Wook Yoo, In-Soo Yoon, Hwayoung Yun, Yunjin Jung. Eletrophilic Chemistry of Tranilast Is Involved in Its Anti-Colitic Activity via Nrf2-HO-1 Pathway Activation. Pharmaceuticals 2021, 14 (11) , 1092. https://doi.org/10.3390/ph14111092
    61. Ana Tapia-Abellán, Diego Angosto-Bazarra, Cristina Alarcón-Vila, María C. Baños, Iva Hafner-Bratkovič, Baldomero Oliva, Pablo Pelegrín. Sensing low intracellular potassium by NLRP3 results in a stable open structure that promotes inflammasome activation. Science Advances 2021, 7 (38) https://doi.org/10.1126/sciadv.abf4468
    62. Yue Wang, Bo Song, Jiebiao Chen, Jinping Cao, Xian Li, Chongde Sun, . Polymethoxyflavones in Citrus Regulate Lipopolysaccharide-Induced Oscillating Decay of Circadian Rhythm Genes by Inhibiting Nlrp3 Expression. Oxidative Medicine and Cellular Longevity 2021, 2021 , 1-15. https://doi.org/10.1155/2021/8419415
    63. Chen Chen, Xiaoqin Liu, Lijie Gong, Tianyu Zhu, Wuxi Zhou, Lingyi Kong, Jianguang Luo. Identification of Tubocapsanolide A as a novel NLRP3 inhibitor for potential treatment of colitis. Biochemical Pharmacology 2021, 190 , 114645. https://doi.org/10.1016/j.bcp.2021.114645
    64. Yijie Song, Yuge Zhao, Yueming Ma, Zhicheng Wang, Lan Rong, Bing Wang, Ning Zhang. Biological functions of NLRP3 inflammasome: A therapeutic target in inflammatory bowel disease. Cytokine & Growth Factor Reviews 2021, 60 , 61-75. https://doi.org/10.1016/j.cytogfr.2021.03.003
    65. Nadire Özenver, Thomas Efferth. Phytochemical inhibitors of the NLRP3 inflammasome for the treatment of inflammatory diseases. Pharmacological Research 2021, 170 , 105710. https://doi.org/10.1016/j.phrs.2021.105710
    66. Biswadeep Das, Chayna Sarkar, Vikram Singh Rawat, Deepjyoti Kalita, Sangeeta Deka, Akash Agnihotri. Promise of the NLRP3 Inflammasome Inhibitors in In Vivo Disease Models. Molecules 2021, 26 (16) , 4996. https://doi.org/10.3390/molecules26164996
    67. Cheng Zhang, Hu Yue, Ping Sun, Lei Hua, Shuli Liang, Yitao Ou, Dan Wu, Xinyi Wu, Hao Chen, Ying Hao, Wenhui Hu, Zhongjin Yang. Discovery of chalcone analogues as novel NLRP3 inflammasome inhibitors with potent anti-inflammation activities. European Journal of Medicinal Chemistry 2021, 219 , 113417. https://doi.org/10.1016/j.ejmech.2021.113417
    68. Simone Gastaldi, Valentina Boscaro, Eleonora Gianquinto, Christina F. Sandall, Marta Giorgis, Elisabetta Marini, Federica Blua, Margherita Gallicchio, Francesca Spyrakis, Justin A. MacDonald, Massimo Bertinaria. Chemical Modulation of the 1-(Piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Scaffold as a Novel NLRP3 Inhibitor. Molecules 2021, 26 (13) , 3975. https://doi.org/10.3390/molecules26133975
    69. Qiu-Ling Chen, Hao-Ran Yin, Qing-Yu He, Ying Wang. Targeting the NLRP3 inflammasome as new therapeutic avenue for inflammatory bowel disease. Biomedicine & Pharmacotherapy 2021, 138 , 111442. https://doi.org/10.1016/j.biopha.2021.111442
    70. Rupak Dey Sarkar, Samraj Sinha, Nabendu Biswas. Manipulation of Inflammasome: A Promising Approach Towards Immunotherapy of Lung Cancer. International Reviews of Immunology 2021, 40 (3) , 171-182. https://doi.org/10.1080/08830185.2021.1876044
    71. Pablo Pelegrin. P2X7 receptor and the NLRP3 inflammasome: Partners in crime. Biochemical Pharmacology 2021, 187 , 114385. https://doi.org/10.1016/j.bcp.2020.114385
    72. Li Wen, Hongliu Yang, Liang Ma, Ping Fu. The roles of NLRP3 inflammasome-mediated signaling pathways in hyperuricemic nephropathy. Molecular and Cellular Biochemistry 2021, 476 (3) , 1377-1386. https://doi.org/10.1007/s11010-020-03997-z
    73. Yuhua Shi, Qian Lv, Mengjie Zheng, Hongxiang Sun, Fushan Shi. NLRP3 inflammasome inhibitor INF39 attenuated NLRP3 assembly in macrophages. International Immunopharmacology 2021, 92 , 107358. https://doi.org/10.1016/j.intimp.2020.107358
    74. Ma Su, Weiwei Wang, Feng Liu, Huanqiu Li. Recent Progress on the Discovery of NLRP3 Inhibitors and their Therapeutic Potential. Current Medicinal Chemistry 2021, 28 (3) , 569-582. https://doi.org/10.2174/0929867327666200123093544
    75. Diego Angosto-Bazarra, Cristina Molina-López, Alejandro Peñín-Franch, Laura Hurtado-Navarro, Pablo Pelegrín. Techniques to Study Inflammasome Activation and Inhibition by Small Molecules. Molecules 2021, 26 (6) , 1704. https://doi.org/10.3390/molecules26061704
    76. Yiming Xu, Matteo Scipioni, Hallie Blevins, Shijun Zhang. Structural insights of sulfonamide-based NLRP3 inflammasome inhibitors: design, synthesis, and biological characterization. Medicinal Chemistry Research 2021, 30 (2) , 473-482. https://doi.org/10.1007/s00044-020-02692-4
    77. Yulong Xu, Yiming Xu, Hallie Blevins, Yu Lan, Yan Liu, Gengyang Yuan, Robin Striar, Julia S. Zagaroli, Darcy R. Tocci, Amelia G. Langan, Can Zhang, Shijun Zhang, Changning Wang. Discovery of carbon-11 labeled sulfonamide derivative: A PET tracer for imaging brain NLRP3 inflammasome. Bioorganic & Medicinal Chemistry Letters 2021, 34 , 127777. https://doi.org/10.1016/j.bmcl.2021.127777
    78. Hongbin Liu, Xiaoyan Zhan, Guang Xu, Zhilei Wang, Ruisheng Li, Yan Wang, Qin Qin, Wei Shi, Xiaorong Hou, Ruichuang Yang, Jian Wang, Xiaohe Xiao, Zhaofang Bai. Cryptotanshinone specifically suppresses NLRP3 inflammasome activation and protects against inflammasome-mediated diseases. Pharmacological Research 2021, 164 , 105384. https://doi.org/10.1016/j.phrs.2020.105384
    79. Maria Sebastian-Valverde, Henry Wu, Md Al Rahim, Roberto Sanchez, Kunal Kumar, Robert J. De Vita, Giulio Maria Pasinetti. Discovery and characterization of small-molecule inhibitors of NLRP3 and NLRC4 inflammasomes. Journal of Biological Chemistry 2021, 296 , 100597. https://doi.org/10.1016/j.jbc.2021.100597
    80. Kaiser Wani, Hind AlHarthi, Amani Alghamdi, Shaun Sabico, Nasser M. Al-Daghri. Role of NLRP3 Inflammasome Activation in Obesity-Mediated Metabolic Disorders. International Journal of Environmental Research and Public Health 2021, 18 (2) , 511. https://doi.org/10.3390/ijerph18020511
    81. Yuefei Jin, Wangquan Ji, Haiyan Yang, Shuaiyin Chen, Weiguo Zhang, Guangcai Duan. Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches. Signal Transduction and Targeted Therapy 2020, 5 (1) https://doi.org/10.1038/s41392-020-00454-7
    82. Ye-Ram Kim, Jae-Sung Kim, Su-Jin Gu, Sungsin Jo, Sojin Kim, Sun Young Kim, Daeun Lee, Kiseok Jang, Hyunah Choo, Tae-Hwan Kim, Jae U. Jung, Sun-Joon Min, Chul-Su Yang. Identification of highly potent and selective inhibitor, TIPTP, of the p22phox-Rubicon axis as a therapeutic agent for rheumatoid arthritis. Scientific Reports 2020, 10 (1) https://doi.org/10.1038/s41598-020-61630-x
    83. Lina Y. El-Sharkawy, David Brough, Sally Freeman. Inhibiting the NLRP3 Inflammasome. Molecules 2020, 25 (23) , 5533. https://doi.org/10.3390/molecules25235533
    84. Li Wang, Arthur V. Hauenstein. The NLRP3 inflammasome: Mechanism of action, role in disease and therapies. Molecular Aspects of Medicine 2020, 76 , 100889. https://doi.org/10.1016/j.mam.2020.100889
    85. Liping Liu, Xueming Xu, Ningjie Zhang, Yening Zhang, Kai Zhao. Acetylase inhibitor SI-2 is a potent anti-inflammatory agent by inhibiting NLRP3 inflammasome activation. International Immunopharmacology 2020, 87 , 106829. https://doi.org/10.1016/j.intimp.2020.106829
    86. Christina F. Sandall, Bjoern K. Ziehr, Justin A. MacDonald. ATP-Binding and Hydrolysis in Inflammasome Activation. Molecules 2020, 25 (19) , 4572. https://doi.org/10.3390/molecules25194572
    87. Alireza Paniri, Haleh Akhavan-Niaki. Emerging role of IL-6 and NLRP3 inflammasome as potential therapeutic targets to combat COVID-19: Role of lncRNAs in cytokine storm modulation. Life Sciences 2020, 257 , 118114. https://doi.org/10.1016/j.lfs.2020.118114
    88. Claudia Penna, Manuela Aragno, Alessia Sofia Cento, Saveria Femminò, Isabella Russo, Federica Dal Bello, Fausto Chiazza, Debora Collotta, Gustavo Ferreira Alves, Massimo Bertinaria, Elisa Zicola, Valentina Mercurio, Claudio Medana, Massimo Collino, Pasquale Pagliaro. Ticagrelor Conditioning Effects Are Not Additive to Cardioprotection Induced by Direct NLRP3 Inflammasome Inhibition: Role of RISK, NLRP3, and Redox Cascades. Oxidative Medicine and Cellular Longevity 2020, 2020 , 1-12. https://doi.org/10.1155/2020/9219825
    89. Petra Sušjan, Duško Lainšček, Žiga Strmšek, Vesna Hodnik, Gregor Anderluh, Iva Hafner‐Bratkovič. Selective inhibition of NLRP3 inflammasome by designed peptide originating from ASC. The FASEB Journal 2020, 34 (8) , 11068-11086. https://doi.org/10.1096/fj.201902938RR
    90. Kelvin Ka-Lok Wu, Samson Wing-Ming Cheung, Kenneth King-Yip Cheng. NLRP3 Inflammasome Activation in Adipose Tissues and Its Implications on Metabolic Diseases. International Journal of Molecular Sciences 2020, 21 (11) , 4184. https://doi.org/10.3390/ijms21114184
    91. Roberta Fusco, Rosalba Siracusa, Tiziana Genovese, Salvatore Cuzzocrea, Rosanna Di Paola. Focus on the Role of NLRP3 Inflammasome in Diseases. International Journal of Molecular Sciences 2020, 21 (12) , 4223. https://doi.org/10.3390/ijms21124223
    92. Giovanni Zito, Marco Buscetta, Maura Cimino, Paola Dino, Fabio Bucchieri, Chiara Cipollina. Cellular Models and Assays to Study NLRP3 Inflammasome Biology. International Journal of Molecular Sciences 2020, 21 (12) , 4294. https://doi.org/10.3390/ijms21124294
    93. Ivan Qi Han Ngui, Agampodi Promoda Perera, Rajaraman Eri. Does NLRP3 Inflammasome and Aryl Hydrocarbon Receptor Play an Interlinked Role in Bowel Inflammation and Colitis-Associated Colorectal Cancer?. Molecules 2020, 25 (10) , 2427. https://doi.org/10.3390/molecules25102427
    94. Yun Chen, Hongbin He, Hua Jiang, Li Li, Zhiyu Hu, Huiying Huang, Qingyan Xu, Rongbin Zhou, Xianming Deng. Discovery and optimization of 4-oxo-2-thioxo-thiazolidinones as NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inhibitors. Bioorganic & Medicinal Chemistry Letters 2020, 30 (7) , 127021. https://doi.org/10.1016/j.bmcl.2020.127021
    95. Shanshan Huang, Jing Che, Qian Chu, Peng Zhang. The Role of NLRP3 Inflammasome in Radiation-Induced Cardiovascular Injury. Frontiers in Cell and Developmental Biology 2020, 8 https://doi.org/10.3389/fcell.2020.00140
    96. Luca Antonioli, Diego Moriconi, Stefano Masi, Dario Bottazzo, Carolina Pellegrini, Matteo Fornai, Marco Anselmino, Ele Ferrannini, Corrado Blandizzi, Stefano Taddei, Monica Nannipieri. Differential Impact of Weight Loss and Glycemic Control on Inflammasome Signaling. Obesity 2020, 28 (3) , 609-615. https://doi.org/10.1002/oby.22734
    97. Yuan Zhou, Tan Ma, Minghao Yan, Xiannan Meng, Jiang Wu, Jie Ding, Xiaodong Han, Dongmei Li. Exposure of DBP in gestation induces inflammation of testicular Sertoli cells in progeny by activating NLRP3 inflammasomes. Science of The Total Environment 2020, 707 , 136139. https://doi.org/10.1016/j.scitotenv.2019.136139
    98. Lotte Spel, Fabio Martinon. Inflammasomes contributing to inflammation in arthritis. Immunological Reviews 2020, 294 (1) , 48-62. https://doi.org/10.1111/imr.12839
    99. Md. Ezazul Haque, Mahbuba Akther, Md. Jakaria, In‐Su Kim, Shofiul Azam, Dong‐Kug Choi. Targeting the Microglial NLRP3 Inflammasome and Its Role in Parkinson's Disease. Movement Disorders 2020, 35 (1) , 20-33. https://doi.org/10.1002/mds.27874
    100. Renren Bai, Xiaokang Jie, Chuansheng Yao, Yuanyuan Xie. Discovery of small-molecule candidates against inflammatory bowel disease. European Journal of Medicinal Chemistry 2020, 185 , 111805. https://doi.org/10.1016/j.ejmech.2019.111805
    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.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect