Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Targeting NLRP3 Inflammasome: Structure, Function, and Inhibitors

Author(s): Shengying Lou, Miaolian Wu* and Sunliang Cui*

Volume 31, Issue 15, 2024

Published on: 02 January, 2024

Page: [2021 - 2051] Pages: 31

DOI: 10.2174/0109298673289984231127062528

Price: $65

Open Access Journals Promotions 2
Abstract

Inflammasomes are multimeric protein complexes that can detect various physiological stimuli and danger signals. As a result, they perform a crucial function in the innate immune response. The NLRP3 inflammasome, as a vital constituent of the inflammasome family, is significant in defending against pathogen invasion and preserving cellhomeostasis. NLRP3 inflammasome dysregulation is connected to various pathological conditions, including inflammatory diseases, cancer, and cardiovascular and neurodegenerative diseases. This profile makes NLRP3 an applicable target for treating related diseases, and therefore, there are rising NLRP3 inhibitors disclosed for therapy. Herein, we summarized the updated advances in the structure, function, and inhibitors of NLRP3 inflammasome. Moreover, we aimed to provide an overview of the existing products and future directions for drug research and development.

Keywords: NLRP3, inflammasome, function, inhibitor, drug discovery, protein complexes.

« Previous Next »
[1]
Martinon, F.; Burns, K.; Tschopp, J. The Inflammasome. Mol. Cell, 2002, 10(2), 417-426.
[http://dx.doi.org/10.1016/S1097-2765(02)00599-3] [PMID: 12191486]
[2]
Zheng, D.; Liwinski, T.; Elinav, E. Inflammasome activation and regulation: Toward a better understanding of complex mechanisms. Cell Discov., 2020, 6(1), 36.
[http://dx.doi.org/10.1038/s41421-020-0167-x] [PMID: 32550001]
[3]
Singh, P.; Kumar, N.; Singh, M.; Kaur, M.; Singh, G.; Narang, A.; Kanwal, A.; Sharma, K.; Singh, B.; Napoli, M.D.; Mastana, S. Neutrophil extracellular traps and NLRP3 inflammasome: A disturbing duo in atherosclerosis, inflammation and atherothrombosis. Vaccines, 2023, 11(2), 261.
[http://dx.doi.org/10.3390/vaccines11020261] [PMID: 36851139]
[4]
Sharma, D.; Kanneganti, T.D. The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation. J. Cell Biol., 2016, 213(6), 617-629.
[http://dx.doi.org/10.1083/jcb.201602089] [PMID: 27325789]
[5]
Christgen, S.; Place, D.E.; Kanneganti, T.D. Toward targeting inflammasomes: Insights into their regulation and activation. Cell Res., 2020, 30(4), 315-327.
[http://dx.doi.org/10.1038/s41422-020-0295-8] [PMID: 32152420]
[6]
Xu, J.; Núñez, G. The NLRP3 inflammasome: Activation and regulation. Trends Biochem. Sci., 2023, 48(4), 331-344.
[http://dx.doi.org/10.1016/j.tibs.2022.10.002] [PMID: 36336552]
[7]
Ohto, U.; Kamitsukasa, Y.; Ishida, H.; Zhang, Z.; Murakami, K.; Hirama, C.; Maekawa, S.; Shimizu, T. Structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation. Proc. Natl. Acad. Sci., 2022, 119(11), e2121353119.
[http://dx.doi.org/10.1073/pnas.2121353119] [PMID: 35254907]
[8]
Tapia-Abellán, A.; Angosto-Bazarra, D.; Alarcón-Vila, C.; Baños, M. C; Hafner-Bratkovič, I.; Oliva, B.; Pelegrín, P. Sensing low intracellular potassium by NLRP3 results in a stable open structure that promotes inflammasome activation. Sci. Adv., 2021, 7, eabf44.
[http://dx.doi.org/10.1126/sciadv.abf4468]
[9]
Dekker, C.; Mattes, H.; Wright, M.; Boettcher, A.; Hinniger, A.; Hughes, N.; Kapps-Fouthier, S.; Eder, J.; Erbel, P.; Stiefl, N.; Mackay, A.; Farady, C.J. Crystal structure of NLRP3 NACHT domain with an inhibitor defines mechanism of inflammasome inhibition. J. Mol. Biol., 2021, 433(24), 167309.
[http://dx.doi.org/10.1016/j.jmb.2021.167309] [PMID: 34687713]
[10]
Sharif, H.; Wang, L.; Wang, W.L.; Magupalli, V.G.; Andreeva, L.; Qiao, Q.; Hauenstein, A.V.; Wu, Z.; Núñez, G.; Mao, Y.; Wu, H. Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome. Nature, 2019, 570(7761), 338-343.
[http://dx.doi.org/10.1038/s41586-019-1295-z] [PMID: 31189953]
[11]
Andreeva, L.; David, L.; Rawson, S.; Shen, C.; Pasricha, T.; Pelegrin, P.; Wu, H. NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation. Cell, 2021, 184(26), 6299-6312.e22.
[http://dx.doi.org/10.1016/j.cell.2021.11.011] [PMID: 34861190]
[12]
Hafner-Bratkovič, I. NLRP3 is its own gatekeeper: A group hug of NLRP3 monomers controls inflammation. Trends Biochem. Sci., 2022, 47(8), 635-637.
[http://dx.doi.org/10.1016/j.tibs.2022.03.014] [PMID: 35382945]
[13]
Hochheiser, I.V.; Pilsl, M.; Hagelueken, G.; Moecking, J.; Marleaux, M.; Brinkschulte, R.; Latz, E.; Engel, C.; Geyer, M. Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3. Nature, 2022, 604(7904), 184-189.
[http://dx.doi.org/10.1038/s41586-022-04467-w] [PMID: 35114687]
[14]
Xiao, L.; Magupalli, V.G.; Wu, H. Cryo-EM structures of the active NLRP3 inflammasome disc. Nature, 2023, 613(7944), 595-600.
[http://dx.doi.org/10.1038/s41586-022-05570-8] [PMID: 36442502]
[15]
Swanson, K.V.; Deng, M.; Ting, J.P.Y. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat. Rev. Immunol., 2019, 19(8), 477-489.
[http://dx.doi.org/10.1038/s41577-019-0165-0] [PMID: 31036962]
[16]
Li, Y.; Fu, T.M.; Lu, A.; Witt, K.; Ruan, J.; Shen, C.; Wu, H. Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1. Proc. Natl. Acad. Sci., 2018, 115(43), 10845-10852.
[http://dx.doi.org/10.1073/pnas.1810524115] [PMID: 30279182]
[17]
Vong, C.T.; Tseng, H.H.L.; Yao, P.; Yu, H.; Wang, S.; Zhong, Z.; Wang, Y. Specific NLRP3 inflammasome inhibitors: Promising therapeutic agents for inflammatory diseases. Drug Discov. Today, 2021, 26(6), 1394-1408.
[http://dx.doi.org/10.1016/j.drudis.2021.02.018] [PMID: 33636340]
[18]
Fu, J.; Wu, H. Structural mechanisms of NLRP3 inflammasome assembly and activation. Annu. Rev. Immunol., 2023, 41(1), 301-316.
[http://dx.doi.org/10.1146/annurev-immunol-081022-021207] [PMID: 36750315]
[19]
Lamkanfi, M.; Dixit, V.M. A new lead to NLRP3 inhibition. J. Exp. Med., 2017, 214(11), 3147-3149.
[http://dx.doi.org/10.1084/jem.20171848] [PMID: 29061692]
[20]
Mangan, M.S.J.; Olhava, E.J.; Roush, W.R.; Seidel, H.M.; Glick, G.D.; Latz, E. Targeting the NLRP3 inflammasome in inflammatory diseases. Nat. Rev. Drug Discov., 2018, 17(8), 588-606.
[http://dx.doi.org/10.1038/nrd.2018.97] [PMID: 30026524]
[21]
Accogli, T.; Hibos, C.; Vegran, F. Canonical and non-canonical functions of NLRP3. J. Adv. Res., 2023, 53, 137-151.
[http://dx.doi.org/10.1016/j.jare.2023.01.001] [PMID: 36610670]
[22]
Yang, Y.; Wang, H.; Kouadir, M.; Song, H.; Shi, F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis., 2019, 10(2), 128.
[http://dx.doi.org/10.1038/s41419-019-1413-8] [PMID: 30755589]
[23]
Paik, S.; Kim, J.K.; Silwal, P.; Sasakawa, C.; Jo, E.K. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell. Mol. Immunol., 2021, 18(5), 1141-1160.
[http://dx.doi.org/10.1038/s41423-021-00670-3] [PMID: 33850310]
[24]
Song, N.; Liu, Z.S.; Xue, W.; Bai, Z.F.; Wang, Q.Y.; Dai, J.; Liu, X.; Huang, Y.J.; Cai, H.; Zhan, X.Y.; Han, Q.Y.; Wang, H.; Chen, Y.; Li, H.Y.; Li, A.L.; Zhang, X.M.; Zhou, T.; Li, T. NLRP3 phosphorylation is an essential priming event for inflammasome activation. Mol. Cell, 2017, 68(1), 185-197.e6.
[http://dx.doi.org/10.1016/j.molcel.2017.08.017] [PMID: 28943315]
[25]
Xu, T.; Yu, W.; Fang, H.; Wang, Z.; Chi, Z.; Guo, X.; Jiang, D.; Zhang, K.; Chen, S.; Li, M.; Guo, Y.; Zhang, J.; Yang, D.; Yu, Q.; Wang, D.; Zhang, X. Ubiquitination of NLRP3 by gp78/Insig-1 restrains NLRP3 inflammasome activation. Cell Death Differ., 2022, 29(8), 1582-1595.
[http://dx.doi.org/10.1038/s41418-022-00947-8] [PMID: 35110683]
[26]
Ge, Q.; Chen, X.; Zhao, Y.; Mu, H.; Zhang, J. Modulatory mechanisms of NLRP3: Potential roles in inflammasome activation. Life Sci., 2021, 267, 118918.
[http://dx.doi.org/10.1016/j.lfs.2020.118918] [PMID: 33352170]
[27]
Gong, T.; Yang, Y.; Jin, T.; Jiang, W.; Zhou, R. Orchestration of NLRP3 inflammasome activation by ion fluxes. Trends Immunol., 2018, 39(5), 393-406.
[http://dx.doi.org/10.1016/j.it.2018.01.009] [PMID: 29452983]
[28]
Chen, M.; Ye, X.; He, X.; Ouyang, D. The signaling pathways regulating NLRP3 inflammasome activation. Inflammation, 2021, 44(4), 1229-1245.
[http://dx.doi.org/10.1007/s10753-021-01439-6] [PMID: 34009550]
[29]
Wang, L.; Sharif, H.; Vora, S.M.; Zheng, Y.; Wu, H. Structures and functions of the inflammasome engine. J. Allergy Clin. Immunol., 2021, 147(6), 2021-2029.
[http://dx.doi.org/10.1016/j.jaci.2021.04.018] [PMID: 34092352]
[30]
Dowling, J.K.; O’Neill, L.A.J. Biochemical regulation of the inflammasome. Crit. Rev. Biochem. Mol. Biol., 2012, 47(5), 424-443.
[http://dx.doi.org/10.3109/10409238.2012.694844] [PMID: 22681257]
[31]
Haneklaus, M.; O’Neill, L.A.J.; Coll, R.C. Modulatory mechanisms controlling the NLRP3 inflammasome in inflammation: Recent developments. Curr. Opin. Immunol., 2013, 25(1), 40-45.
[http://dx.doi.org/10.1016/j.coi.2012.12.004] [PMID: 23305783]
[32]
Kayagaki, N.; Warming, S.; Lamkanfi, M.; Walle, L.V.; Louie, S.; Dong, J.; Newton, K.; Qu, Y.; Liu, J.; Heldens, S.; Zhang, J.; Lee, W.P.; Roose-Girma, M.; Dixit, V.M. Non-canonical inflammasome activation targets caspase-11. Nature, 2011, 479(7371), 117-121.
[http://dx.doi.org/10.1038/nature10558] [PMID: 22002608]
[33]
Shi, J.; Zhao, Y.; Wang, Y.; Gao, W.; Ding, J.; Li, P.; Hu, L.; Shao, F. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature, 2014, 514(7521), 187-192.
[http://dx.doi.org/10.1038/nature13683] [PMID: 25119034]
[34]
Moretti, J.; Jia, B.; Hutchins, Z.; Roy, S.; Yip, H.; Wu, J.; Shan, M.; Jaffrey, S.R.; Coers, J.; Blander, J.M. Caspase-11 interaction with NLRP3 potentiates the noncanonical activation of the NLRP3 inflammasome. Nat. Immunol., 2022, 23(5), 705-717.
[http://dx.doi.org/10.1038/s41590-022-01192-4] [PMID: 35487985]
[35]
Yang, Z.H.; Han, J. Dual ligand engagement for noncanonical inflammasome activation. Nat. Immunol., 2022, 23(5), 651-653.
[http://dx.doi.org/10.1038/s41590-022-01188-0] [PMID: 35487984]
[36]
Gaidt, M.M.; Ebert, T.S.; Chauhan, D.; Schmidt, T.; Schmid-Burgk, J.L.; Rapino, F.; Robertson, A.A.B.; Cooper, M.A.; Graf, T.; Hornung, V. Human monocytes engage an alternative inflammasome pathway. Immunity, 2016, 44(4), 833-846.
[http://dx.doi.org/10.1016/j.immuni.2016.01.012] [PMID: 27037191]
[37]
Huang, Y.; Xu, W.; Zhou, R. NLRP3 inflammasome activation and cell death. Cell. Mol. Immunol., 2021, 18(9), 2114-2127.
[http://dx.doi.org/10.1038/s41423-021-00740-6] [PMID: 34321623]
[38]
Li, Y.; Huang, H.; Liu, B.; Zhang, Y.; Pan, X.; Yu, X.Y.; Shen, Z.; Song, Y.H. Inflammasomes as therapeutic targets in human diseases. Signal Transduct. Target. Ther., 2021, 6(1), 247.
[http://dx.doi.org/10.1038/s41392-021-00650-z] [PMID: 34210954]
[39]
Moltrasio, C.; Romagnuolo, M.; Marzano, A.V. NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies. Front. Immunol., 2022, 13, 1007705.
[http://dx.doi.org/10.3389/fimmu.2022.1007705] [PMID: 36275641]
[40]
de Torre-Minguela, C.; Mesa del Castillo, P.; Pelegrín, P. The NLRP3 and pyrin inflammasomes: Implications in the pathophysiology of autoinflammatory diseases. Front. Immunol., 2017, 8, 43.
[http://dx.doi.org/10.3389/fimmu.2017.00043] [PMID: 28191008]
[41]
de Jesus, A.A.; Canna, S.W.; Liu, Y.; Goldbach-Mansky, R. Molecular mechanisms in genetically defined autoinflammatory diseases: Disorders of amplified danger signaling. Annu. Rev. Immunol., 2015, 33(1), 823-874.
[http://dx.doi.org/10.1146/annurev-immunol-032414-112227] [PMID: 25706096]
[42]
Booshehri, L.M.; Hoffman, H.M. CAPS and NLRP3. J. Clin. Immunol., 2019, 39(3), 277-286.
[http://dx.doi.org/10.1007/s10875-019-00638-z] [PMID: 31077002]
[43]
Cuisset, L.; Jeru, I.; Dumont, B.; Fabre, A.; Cochet, E.; Le Bozec, J.; Delpech, M.; Amselem, S.; Touitou, I. Mutations in the autoinflammatory cryopyrin-associated periodic syndrome gene: Epidemiological study and lessons from eight years of genetic analysis in France. Ann. Rheum. Dis., 2011, 70(3), 495-499.
[http://dx.doi.org/10.1136/ard.2010.138420] [PMID: 21109514]
[44]
Theodoropoulou, K.; Spel, L.; Zaffalon, L.; Delacrétaz, M.; Hofer, M.; Martinon, F. NLRP3 leucine-rich repeats control induced and spontaneous inflammasome activation in cryopyrin-associated periodic syndrome. J. Allergy Clin. Immunol., 2023, 151(1), 222-232.e9.
[http://dx.doi.org/10.1016/j.jaci.2022.08.019] [PMID: 36075321]
[45]
Guan, Q. A comprehensive review and update on the pathogenesis of inflammatory bowel disease. J. Immunol. Res., 2019, 2019, 1-16.
[http://dx.doi.org/10.1155/2019/7247238] [PMID: 31886308]
[46]
Bauer, C.; Duewell, P.; Mayer, C.; Lehr, H.A.; Fitzgerald, K.A.; Dauer, M.; Tschopp, J.; Endres, S.; Latz, E.; Schnurr, M. Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut, 2010, 59(9), 1192-1199.
[http://dx.doi.org/10.1136/gut.2009.197822] [PMID: 20442201]
[47]
Liu, L.; Dong, Y.; Ye, M.; Jin, S.; Yang, J.; Joosse, M.E.; Sun, Y.; Zhang, J.; Lazarev, M.; Brant, S.R.; Safar, B.; Marohn, M.; Mezey, E.; Li, X. The pathogenic role of NLRP3 inflammasome activation in inflammatory bowel diseases of both mice and humans. J. Crohn’s Colitis, 2017, 11(6), 737-750.
[PMID: 27993998]
[48]
Wang, S.L.; Zhang, M.M.; Zhou, H.; Su, G.Q.; Ding, Y.; Xu, G.H.; Wang, X.; Li, C.F.; Huang, W.F.; Yi, L.T. Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation. Biomed. J., 2023, 46(5), 100580.
[http://dx.doi.org/10.1016/j.bj.2023.01.004] [PMID: 36758943]
[49]
Chen, Q.L.; Yin, H.R.; He, Q.Y.; Wang, Y. Targeting the NLRP3 inflammasome as new therapeutic avenue for inflammatory bowel disease. Biomed. Pharmacother., 2021, 138, 111442.
[http://dx.doi.org/10.1016/j.biopha.2021.111442] [PMID: 33667791]
[50]
Zaki, M.H.; Boyd, K.L.; Vogel, P.; Kastan, M.B.; Lamkanfi, M.; Kanneganti, T.D. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity, 2010, 32(3), 379-391.
[http://dx.doi.org/10.1016/j.immuni.2010.03.003] [PMID: 20303296]
[51]
Song, Y.; Zhao, Y.; Ma, Y.; Wang, Z.; Rong, L.; Wang, B.; Zhang, N. Biological functions of NLRP3 inflammasome: A therapeutic target in inflammatory bowel disease. Cytokine Growth Factor Rev., 2021, 60, 61-75.
[http://dx.doi.org/10.1016/j.cytogfr.2021.03.003] [PMID: 33773897]
[52]
Zhen, Y.; Zhang, H. NLRP3 inflammasome and inflammatory bowel disease. Front. Immunol., 2019, 10, 276.
[http://dx.doi.org/10.3389/fimmu.2019.00276] [PMID: 30873162]
[53]
Toldo, S.; Mezzaroma, E.; Buckley, L.F.; Potere, N.; Di Nisio, M.; Biondi-Zoccai, G.; Van Tassell, B.W.; Abbate, A. Targeting the NLRP3 inflammasome in cardiovascular diseases. Pharmacol. Ther., 2022, 236, 108053.
[http://dx.doi.org/10.1016/j.pharmthera.2021.108053] [PMID: 34906598]
[54]
Grebe, A.; Hoss, F.; Latz, E. NLRP3 inflammasome and the IL-1 pathway in atherosclerosis. Circ. Res., 2018, 122(12), 1722-1740.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.311362] [PMID: 29880500]
[55]
Baldrighi, M.; Mallat, Z.; Li, X. NLRP3 inflammasome pathways in atherosclerosis. Atherosclerosis, 2017, 267, 127-138.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.10.027] [PMID: 29126031]
[56]
Poznyak, A.V.; Melnichenko, A.A.; Wetzker, R.; Gerasimova, E.V.; Orekhov, A.N. NLPR3 inflammasomes and their significance for atherosclerosis. Biomedicines, 2020, 8(7), 205.
[http://dx.doi.org/10.3390/biomedicines8070205] [PMID: 32664349]
[57]
Jiang, C.; Xie, S.; Yang, G.; Wang, N. Spotlight on NLRP3 inflammasome: Role in pathogenesis and therapies of atherosclerosis. J. Inflamm. Res., 2021, 14, 7143-7172.
[http://dx.doi.org/10.2147/JIR.S344730] [PMID: 34992411]
[58]
Hoseini, Z.; Sepahvand, F.; Rashidi, B.; Sahebkar, A.; Masoudifar, A.; Mirzaei, H. NLRP3 inflammasome: Its regulation and involvement in atherosclerosis. J. Cell. Physiol., 2018, 233(3), 2116-2132.
[http://dx.doi.org/10.1002/jcp.25930] [PMID: 28345767]
[59]
Duewell, P.; Kono, H.; Rayner, K.J.; Sirois, C.M.; Vladimer, G.; Bauernfeind, F.G.; Abela, G.S.; Franchi, L.; Nuñez, G.; Schnurr, M.; Espevik, T.; Lien, E.; Fitzgerald, K.A.; Rock, K.L.; Moore, K.J.; Wright, S.D.; Hornung, V.; Latz, E. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature, 2010, 464(7293), 1357-1361.
[http://dx.doi.org/10.1038/nature08938] [PMID: 20428172]
[60]
Zheng, F.; Xing, S.; Gong, Z.; Mu, W.; Xing, Q. Cancer statistics. Cancer J. Clin., 2014, 73, 17-48.
[61]
Siegel, R.L.; Miller, K.D.; Wagle, N.S.; Jemal, A. Cancer statistics, 2023. CA Cancer J. Clin., 2023, 73(1), 17-48.
[http://dx.doi.org/10.3322/caac.21763] [PMID: 36633525]
[62]
Siegel, R.; Ma, J.; Zou, Z.; Jemal, A. Cancer statistics, 2014. CA Cancer J. Clin., 2014, 64(1), 9-29.
[http://dx.doi.org/10.3322/caac.21208] [PMID: 24399786]
[63]
Moossavi, M.; Parsamanesh, N.; Bahrami, A.; Atkin, S.L.; Sahebkar, A. Role of the NLRP3 inflammasome in cancer. Mol. Cancer, 2018, 17(1), 158.
[http://dx.doi.org/10.1186/s12943-018-0900-3] [PMID: 30447690]
[64]
Dostert, C.; Pétrilli, V.; Van Bruggen, R.; Steele, C.; Mossman, B.T.; Tschopp, J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science, 2008, 320(5876), 674-677.
[http://dx.doi.org/10.1126/science.1156995] [PMID: 18403674]
[65]
Cox, L.A., Jr Dose-response modeling of NLRP3 inflammasome-mediated diseases: Asbestos, lung cancer, and malignant mesothelioma as examples. Crit. Rev. Toxicol., 2019, 49(7), 614-635.
[http://dx.doi.org/10.1080/10408444.2019.1692779] [PMID: 31905042]
[66]
Wang, Y.; Kong, H.; Zeng, X.; Liu, W.; Wang, Z.; Yan, X.; Wang, H.; Xie, W. Activation of NLRP3 inflammasome enhances the proliferation and migration of A549 lung cancer cells. Oncol. Rep., 2016, 35(4), 2053-2064.
[http://dx.doi.org/10.3892/or.2016.4569] [PMID: 26782741]
[67]
Faria, S.S.; Costantini, S.; de Lima, V.C.C.; de Andrade, V.P.; Rialland, M.; Cedric, R.; Budillon, A.; Magalhães, K.G. NLRP3 inflammasome-mediated cytokine production and pyroptosis cell death in breast cancer. J. Biomed. Sci., 2021, 28(1), 26.
[http://dx.doi.org/10.1186/s12929-021-00724-8] [PMID: 33840390]
[68]
Ershaid, N.; Sharon, Y.; Doron, H.; Raz, Y.; Shani, O.; Cohen, N.; Monteran, L.; Leider-Trejo, L.; Ben-Shmuel, A.; Yassin, M.; Gerlic, M.; Ben-Baruch, A.; Pasmanik-Chor, M.; Apte, R.; Erez, N. NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis. Nat. Commun., 2019, 10(1), 4375.
[http://dx.doi.org/10.1038/s41467-019-12370-8] [PMID: 31558756]
[69]
Wang, Y.; Zhang, H.; Xu, Y.; Peng, T.; Meng, X.; Zou, F. NLRP3 induces the autocrine secretion of IL-1β to promote epithelial–mesenchymal transition and metastasis in breast cancer. Biochem. Biophys. Res. Commun., 2021, 560, 72-79.
[http://dx.doi.org/10.1016/j.bbrc.2021.04.122] [PMID: 33975248]
[70]
Guo, B.; Fu, S.; Zhang, J.; Liu, B.; Li, Z. Targeting inflammasome/IL-1 pathways for cancer immunotherapy. Sci. Rep., 2016, 6(1), 36107.
[http://dx.doi.org/10.1038/srep36107] [PMID: 27786298]
[71]
Missiroli, S.; Perrone, M.; Boncompagni, C.; Borghi, C.; Campagnaro, A.; Marchetti, F.; Anania, G.; Greco, P.; Fiorica, F.; Pinton, P.; Giorgi, C. Targeting the NLRP3 inflammasome as a new therapeutic option for overcoming cancer. Cancers, 2021, 13(10), 2297.
[http://dx.doi.org/10.3390/cancers13102297] [PMID: 34064909]
[72]
Peek, R.M., Jr Orchestration of aberrant epithelial signaling by Helicobacter pylori CagA. Sci. STKE, 2005, 2005(277), pe14.
[http://dx.doi.org/10.1126/stke.2772005pe14] [PMID: 15798102]
[73]
Lamb, A.; Chen, L.F. Role of the Helicobacter pylori -induced inflammatory response in the development of gastric cancer. J. Cell. Biochem., 2013, 114(3), 491-497.
[http://dx.doi.org/10.1002/jcb.24389] [PMID: 22961880]
[74]
Semper, R.P.; Mejías-Luque, R.; Groß, C.; Anderl, F.; Müller, A.; Vieth, M.; Busch, D.H.; Prazeres da Costa, C.; Ruland, J.; Groß, O.; Gerhard, M. Helicobacter pylori-induced IL-1β secretion in innate immune cells is regulated by the NLRP3 inflammasome and requires the cag pathogenicity island. J. Immunol., 2014, 193(7), 3566-3576.
[http://dx.doi.org/10.4049/jimmunol.1400362] [PMID: 25172489]
[75]
Deans, D A C.; Wigmore, S.J.; Gilmour, H.; Paterson-Brown, S.; Ross, J.A.; Fearon, K.C.H. Elevated tumour interleukin-1β is associated with systemic inflammation: a marker of reduced survival in gastro-oesophageal cancer. Br. J. Cancer, 2006, 95(11), 1568-1575.
[http://dx.doi.org/10.1038/sj.bjc.6603446] [PMID: 17088911]
[76]
Bagheri, V.; Memar, B.; Momtazi, A.A.; Sahebkar, A.; Gholamin, M.; Abbaszadegan, M.R. Cytokine networks and their association with Helicobacter pylori infection in gastric carcinoma. J. Cell. Physiol., 2018, 233(4), 2791-2803.
[http://dx.doi.org/10.1002/jcp.25822] [PMID: 28121015]
[77]
Li, S.; Liang, X.; Ma, L.; Shen, L.; Li, T.; Zheng, L.; Sun, A.; Shang, W.; Chen, C.; Zhao, W.; Jia, J. MiR-22 sustains NLRP3 expression and attenuates H. pylori-induced gastric carcinogenesis. Oncogene, 2018, 37(7), 884-896.
[http://dx.doi.org/10.1038/onc.2017.381] [PMID: 29059152]
[78]
Karki, R.; Kanneganti, T.D. Diverging inflammasome signals in tumorigenesis and potential targeting. Nat. Rev. Cancer, 2019, 19(4), 197-214.
[http://dx.doi.org/10.1038/s41568-019-0123-y] [PMID: 30842595]
[79]
Hamarsheh, S.; Zeiser, R. NLRP3 inflammasome activation in cancer: A double-edged sword. Front. Immunol., 2020, 11, 1444.
[http://dx.doi.org/10.3389/fimmu.2020.01444] [PMID: 32733479]
[80]
Zaki, M.H.; Vogel, P.; Body-Malapel, M.; Lamkanfi, M.; Kanneganti, T.D. IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation. J. Immunol., 2010, 185(8), 4912-4920.
[http://dx.doi.org/10.4049/jimmunol.1002046] [PMID: 20855874]
[81]
Sharma, B.R.; Kanneganti, T.D. NLRP3 inflammasome in cancer and metabolic diseases. Nat. Immunol., 2021, 22(5), 550-559.
[http://dx.doi.org/10.1038/s41590-021-00886-5] [PMID: 33707781]
[82]
McCarron, R.M.; Shapiro, B.; Rawles, J. Luo, J. Depression. Ann. Intern. Med., 2021, 174(5), ITC65-ITC80.
[http://dx.doi.org/10.7326/AITC202105180] [PMID: 33971098]
[83]
Miller, A.H.; Maletic, V.; Raison, C.L. Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biol. Psychiatry, 2009, 65(9), 732-741.
[http://dx.doi.org/10.1016/j.biopsych.2008.11.029] [PMID: 19150053]
[84]
Iwata, M.; Ota, K.T.; Duman, R.S. The inflammasome: Pathways linking psychological stress, depression, and systemic illnesses. Brain Behav. Immun., 2013, 31, 105-114.
[http://dx.doi.org/10.1016/j.bbi.2012.12.008] [PMID: 23261775]
[85]
Zhang, Y.; Liu, L.; Peng, Y.L.; Liu, Y.Z.; Wu, T.Y.; Shen, X.L.; Zhou, J.R.; Sun, D.Y.; Huang, A.J.; Wang, X.; Wang, Y.X.; Jiang, C.L. Involvement of inflammasome activation in lipopolysaccharide-induced mice depressive-like behaviors. CNS Neurosci. Ther., 2014, 20(2), 119-124.
[http://dx.doi.org/10.1111/cns.12170] [PMID: 24279434]
[86]
Alcocer-Gómez, E.; Ulecia-Morón, C.; Marín-Aguilar, F.; Rybkina, T.; Casas-Barquero, N.; Ruiz-Cabello, J.; Ryffel, B.; Apetoh, L.; Ghiringhelli, F.; Bullón, P.; Sánchez-Alcazar, J.A.; Carrión, A.M.; Cordero, M.D. Stress-induced depressive behaviors require a functional NLRP3 inflammasome. Mol. Neurobiol., 2016, 53(7), 4874-4882.
[http://dx.doi.org/10.1007/s12035-015-9408-7] [PMID: 26362308]
[87]
Kaufmann, F.N.; Costa, A.P.; Ghisleni, G.; Diaz, A.P.; Rodrigues, A.L.S.; Peluffo, H.; Kaster, M.P. NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings. Brain Behav. Immun., 2017, 64, 367-383.
[http://dx.doi.org/10.1016/j.bbi.2017.03.002] [PMID: 28263786]
[88]
Liang, T.; Zhang, Y.; Wu, S.; Chen, Q.; Wang, L. The role of NLRP3 inflammasome in Alzheimer’s disease and potential therapeutic targets. Front. Pharmacol., 2022, 13, 845185.
[http://dx.doi.org/10.3389/fphar.2022.845185] [PMID: 35250595]
[89]
Heneka, M.T.; Kummer, M.P.; Stutz, A.; Delekate, A.; Schwartz, S.; Vieira-Saecker, A.; Griep, A.; Axt, D.; Remus, A.; Tzeng, T.C.; Gelpi, E.; Halle, A.; Korte, M.; Latz, E.; Golenbock, D.T. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature, 2013, 493(7434), 674-678.
[http://dx.doi.org/10.1038/nature11729] [PMID: 23254930]
[90]
Saresella, M.; La Rosa, F.; Piancone, F.; Zoppis, M.; Marventano, I.; Calabrese, E.; Rainone, V.; Nemni, R.; Mancuso, R.; Clerici, M. The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer’s disease. Mol. Neurodegener., 2016, 11(1), 23.
[http://dx.doi.org/10.1186/s13024-016-0088-1] [PMID: 26939933]
[91]
Ahmed, M.E.; Iyer, S.; Thangavel, R.; Kempuraj, D.; Selvakumar, G.P.; Raikwar, S.P.; Zaheer, S.; Zaheer, A. Co-Localization of glia maturation factor with NLRP3 inflammasome and autophagosome markers in human Alzheimer’s disease brain. J. Alzheimers Dis., 2017, 60(3), 1143-1160.
[http://dx.doi.org/10.3233/JAD-170634] [PMID: 28984607]
[92]
Milner, M.T.; Maddugoda, M.; Götz, J.; Burgener, S.S.; Schroder, K. The NLRP3 inflammasome triggers sterile neuroinflammation and Alzheimer’s disease. Curr. Opin. Immunol., 2021, 68, 116-124.
[http://dx.doi.org/10.1016/j.coi.2020.10.011] [PMID: 33181351]
[93]
Feng, Y.S.; Tan, Z.X.; Wu, L.Y.; Dong, F.; Zhang, F. The involvement of NLRP3 inflammasome in the treatment of Alzheimer’s disease. Ageing Res. Rev., 2020, 64, 101192.
[http://dx.doi.org/10.1016/j.arr.2020.101192] [PMID: 33059089]
[94]
Ding, S.; Xu, S.; Ma, Y.; Liu, G.; Jang, H.; Fang, J. Modulatory mechanisms of the NLRP3 inflammasomes in diabetes. Biomolecules, 2019, 9(12), 850.
[http://dx.doi.org/10.3390/biom9120850] [PMID: 31835423]
[95]
Esser, N.; L’homme, L.; De Roover, A.; Kohnen, L.; Scheen, A.J.; Moutschen, M.; Piette, J.; Legrand-Poels, S.; Paquot, N. Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue. Diabetologia, 2013, 56(11), 2487-2497.
[http://dx.doi.org/10.1007/s00125-013-3023-9]
[96]
Gora, I.M.; Ciechanowska, A.; Ladyzynski, P. NLRP3 inflammasome at the interface of inflammation, endothelial dysfunction, and type 2 diabetes. Cells, 2021, 10(2), 314.
[http://dx.doi.org/10.3390/cells10020314] [PMID: 33546399]
[97]
Lamkanfi, M.; Mueller, J.L.; Vitari, A.C.; Misaghi, S.; Fedorova, A.; Deshayes, K.; Lee, W.P.; Hoffman, H.M.; Dixit, V.M. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J. Cell Biol., 2009, 187(1), 61-70.
[http://dx.doi.org/10.1083/jcb.200903124] [PMID: 19805629]
[98]
Carvalho, A.M.; Novais, F.O.; Paixão, C.S.; de Oliveira, C.I.; Machado, P.R.L.; Carvalho, L.P.; Scott, P.; Carvalho, E.M. Glyburide, a NLRP3 inhibitor, decreases inflammatory response and is a candidate to reduce pathology in leishmania Braziliensis infection. J. Invest. Dermatol., 2020, 140(1), 246-249.e2.
[http://dx.doi.org/10.1016/j.jid.2019.05.025] [PMID: 31252034]
[99]
Zhang, G.; Lin, X.; Zhang, S.; Xiu, H.; Pan, C.; Cui, W. A protective role of glibenclamide in inflammation-associated injury. Mediat. Inflamm., 2017, 3578702.
[100]
Marchetti, C.; Chojnacki, J.; Toldo, S.; Mezzaroma, E.; Tranchida, N.; Rose, S.W.; Federici, M.; Van Tassell, B.W.; Zhang, S.; Abbate, A. A novel pharmacologic inhibitor of the NLRP3 inflammasome limits myocardial injury after ischemia-reperfusion in the mouse. J. Cardiovasc. Pharmacol., 2014, 63(4), 316-322.
[http://dx.doi.org/10.1097/FJC.0000000000000053] [PMID: 24336017]
[101]
Marchetti, C.; Toldo, S.; Chojnacki, J.; Mezzaroma, E.; Liu, K.; Salloum, F.N.; Nordio, A.; Carbone, S.; Mauro, A.G.; Das, A.; Zalavadia, A.A.; Halquist, M.S.; Federici, M.; Van Tassell, B.W.; Zhang, S.; Abbate, A. Pharmacologic inhibition of the NLRP3 inflammasome preserves cardiac function after ischemic and nonischemic injury in the mouse. J. Cardiovasc. Pharmacol., 2015, 66(1), 1-8.
[http://dx.doi.org/10.1097/FJC.0000000000000247] [PMID: 25915511]
[102]
Guo, C.; Fulp, J.W.; Jiang, Y.; Li, X.; Chojnacki, J.E.; Wu, J.; Wang, X.Y.; Zhang, S. Development and characterization of a hydroxyl-sulfonamide analogue, 5-chloro-N-[2-(4-hydroxysulfamoyl-phenyl)-ethyl]-2-methoxy-benzamide, as a novel NLRP3 inflammasome inhibitor for potential treatment of multiple sclerosis. ACS Chem. Neurosci., 2017, 8(10), 2194-2201.
[http://dx.doi.org/10.1021/acschemneuro.7b00124] [PMID: 28653829]
[103]
Yin, J.; Zhao, F.; Chojnacki, J.E.; Fulp, J.; Klein, W.L.; Zhang, S.; Zhu, X. NLRP3 inflammasome inhibitor ameliorates amyloid pathology in a mouse model of Alzheimer’s disease. Mol. Neurobiol., 2018, 55(3), 1977-1987.
[http://dx.doi.org/10.1007/s12035-017-0467-9] [PMID: 28255908]
[104]
Kuwar, R.; Rolfe, A.; Di, L.; Xu, H.; He, L.; Jiang, Y.; Zhang, S.; Sun, D. A novel small molecular NLRP3 inflammasome inhibitor alleviates neuroinflammatory response following traumatic brain injury. J. Neuroinflammation, 2019, 16(1), 81.
[http://dx.doi.org/10.1186/s12974-019-1471-y] [PMID: 30975164]
[105]
Fulp, J.; He, L.; Toldo, S.; Jiang, Y.; Boice, A.; Guo, C.; Li, X.; Rolfe, A.; Sun, D.; Abbate, A.; Wang, X.Y.; Zhang, S. Structural insights of benzenesulfonamide analogues as NLRP3 inflammasome inhibitors: Design, synthesis, and biological characterization. J. Med. Chem., 2018, 61(12), 5412-5423.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00733] [PMID: 29877709]
[106]
Jiang, Y.; He, L.; Green, J.; Blevins, H.; Guo, C.; Patel, S.H.; Halquist, M.S.; McRae, M.; Venitz, J.; Wang, X.Y.; Zhang, S. Discovery of second-generation NLRP3 inflammasome inhibitors: Design, synthesis, and biological characterization. J. Med. Chem., 2019, 62(21), 9718-9731.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01155] [PMID: 31626545]
[107]
Xu, Y.; Xu, Y.; Blevins, H.; Guo, C.; Biby, S.; Wang, X.Y.; Wang, C.; Zhang, S. Development of sulfonamide-based NLRP3 inhibitors: Further modifications and optimization through structure-activity relationship studies. Eur. J. Med. Chem., 2022, 238, 114468.
[http://dx.doi.org/10.1016/j.ejmech.2022.114468] [PMID: 35635948]
[108]
Perregaux, D.G.; McNiff, P.; Laliberte, R.; Hawryluk, N.; Peurano, H.; Stam, E.; Eggler, J.; Griffiths, R.; Dombroski, M.A.; Gabel, C.A. Identification and characterization of a novel class of interleukin-1 post-translational processing inhibitors. J. Pharmacol. Exp. Ther., 2001, 299(1), 187-197.
[PMID: 11561079]
[109]
Laliberte, R.E.; Perregaux, D.G.; Hoth, L.R.; Rosner, P.J.; Jordan, C.K.; Peese, K.M.; Eggler, J.F.; Dombroski, M.A.; Geoghegan, K.F.; Gabel, C.A. Glutathione s-transferase omega 1-1 is a target of cytokine release inhibitory drugs and may be responsible for their effect on interleukin-1β posttranslational processing. J. Biol. Chem., 2003, 278(19), 16567-16578.
[http://dx.doi.org/10.1074/jbc.M211596200] [PMID: 12624100]
[110]
Coll, R.C.; O’Neill, L.A.J.; Butler, M.; Cooper, M.; O’Neill, L.A. The cytokine release inhibitory drug CRID3 targets ASC oligomerisation in the NLRP3 and AIM2 inflammasomes. PLoS One, 2011, 6(12), e29539.
[http://dx.doi.org/10.1371/journal.pone.0029539] [PMID: 22216309]
[111]
Tapia-Abellán, A.; Angosto-Bazarra, D.; Martínez-Banaclocha, H.; de Torre-Minguela, C.; Cerón-Carrasco, J.P.; Pérez-Sánchez, H.; Arostegui, J.I.; Pelegrin, P. MCC950 closes the active conformation of NLRP3 to an inactive state. Nat. Chem. Biol., 2019, 15(6), 560-564.
[http://dx.doi.org/10.1038/s41589-019-0278-6] [PMID: 31086329]
[112]
Coll, R.C.; Hill, J.R.; Day, C.J.; Zamoshnikova, A.; Boucher, D.; Massey, N.L.; Chitty, J.L.; Fraser, J.A.; Jennings, M.P.; Robertson, A.A.B.; Schroder, K. MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nat. Chem. Biol., 2019, 15(6), 556-559.
[http://dx.doi.org/10.1038/s41589-019-0277-7] [PMID: 31086327]
[113]
Corcoran, S.E.; Halai, R.; Cooper, M.A. Pharmacological inhibition of the Nod-Like receptor family pyrin domain containing 3 inflammasome with MCC950. Pharmacol. Rev., 2021, 73(3), 968-1000.
[http://dx.doi.org/10.1124/pharmrev.120.000171] [PMID: 34117094]
[114]
Salla, M.; Butler, M.S.; Pelingon, R.; Kaeslin, G.; Croker, D.E.; Reid, J.C.; Baek, J.M.; Bernhardt, P.V.; Gillam, E.M.J.; Cooper, M.A.; Robertson, A.A.B. Identification, synthesis, and biological evaluation of the major human metabolite of NLRP3 inflammasome inhibitor MCC950. ACS Med. Chem. Lett., 2016, 7(12), 1034-1038.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00198] [PMID: 27994733]
[115]
Li, H.; Guan, Y.; Liang, B.; Ding, P.; Hou, X.; Wei, W.; Ma, Y. Therapeutic potential of MCC950, a specific inhibitor of NLRP3 inflammasome. Eur. J. Pharmacol., 2022, 928, 175091.
[http://dx.doi.org/10.1016/j.ejphar.2022.175091] [PMID: 35714692]
[116]
Hill, J.R.; Coll, R.C.; Sue, N.; Reid, J.C.; Dou, J.; Holley, C.L.; Pelingon, R.; Dickinson, J.B.; Biden, T.J.; Schroder, K.; Cooper, M.A.; Robertson, A.A.B. Sulfonylureas as concomitant insulin secretagogues and NLRP3 inflammasome inhibitors. ChemMedChem, 2017, 12(17), 1449-1457.
[http://dx.doi.org/10.1002/cmdc.201700270] [PMID: 28703484]
[117]
Agarwal, S.; Pethani, J.P.; Shah, H.A.; Vyas, V.; Sasane, S.; Bhavsar, H.; Bandyopadhyay, D.; Giri, P.; Viswanathan, K.; Jain, M.R.; Sharma, R. Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor. Bioorg. Med. Chem. Lett., 2020, 30(21), 127571.
[http://dx.doi.org/10.1016/j.bmcl.2020.127571] [PMID: 32980515]
[118]
McBride, C.; Trzoss, L.; Povero, D.; Lazic, M.; Ambrus-Aikelin, G.; Santini, A.; Pranadinata, R.; Bain, G.; Stansfield, R.; Stafford, J.A.; Veal, J.; Takahashi, R.; Ly, J.; Chen, S.; Liu, L.; Nespi, M.; Blake, R.; Katewa, A.; Kleinheinz, T.; Sujatha-Bhaskar, S.; Ramamoorthi, N.; Sims, J.; McKenzie, B.; Chen, M.; Ultsch, M.; Johnson, M.; Murray, J.; Ciferri, C.; Staben, S.T.; Townsend, M.J.; Stivala, C.E. Overcoming Preclinical Safety Obstacles to Discover (S)- N -((1,2,3,5,6,7-Hexahydro- s -indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5 H -pyrazolo[5,1- b][1,3]oxazine-3-sulfonamide (GDC-2394): A Potent and Selective NLRP3 Inhibitor. J. Med. Chem., 2022, 65(21), 14721-14739.
[http://dx.doi.org/10.1021/acs.jmedchem.2c01250] [PMID: 36279149]
[119]
Agarwal, S.; Sasane, S.; Shah, H.A.; Pethani, J.P.; Deshmukh, P.; Vyas, V.; Iyer, P.; Bhavsar, H.; Viswanathan, K.; Bandyopadhyay, D.; Giri, P.; Mahapatra, J.; Chatterjee, A.; Jain, M.R.; Sharma, R. Discovery of N-cyano-sulfoximineurea derivatives as potent and orally bioavailable NLRP3 inflammasome inhibitors. ACS Med. Chem. Lett., 2020, 11(4), 414-418.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00433] [PMID: 32292543]
[120]
Harrison, D.; Boutard, N.; Brzozka, K.; Bugaj, M.; Chmielewski, S.; Cierpich, A.; Doedens, J.R.; Fabritius, C.H.R.Y.; Gabel, C.A.; Galezowski, M.; Kowalczyk, P.; Levenets, O.; Mroczkowska, M.; Palica, K.; Porter, R.A.; Schultz, D.; Sowinska, M.; Topolnicki, G.; Urbanski, P.; Woyciechowski, J.; Watt, A.P. Discovery of a series of ester-substituted NLRP3 inflammasome inhibitors. Bioorg. Med. Chem. Lett., 2020, 30(23), 127560.
[http://dx.doi.org/10.1016/j.bmcl.2020.127560] [PMID: 32956781]
[121]
Albanese, V.; Missiroli, S.; Perrone, M.; Fabbri, M.; Boncompagni, C.; Pacifico, S.; De Ventura, T.; Ciancetta, A.; Dondio, G.; Kricek, F.; Pinton, P.; Guerrini, R.; Preti, D.; Giorgi, C. Novel aryl sulfonamide derivatives as NLRP3 inflammasome inhibitors for the potential treatment of cancer. J. Med. Chem., 2023, 66(7), 5223-5241.
[http://dx.doi.org/10.1021/acs.jmedchem.3c00175] [PMID: 36972104]
[122]
Li, W.; Cao, Z.; Cheng, J.; Chen, F.; Li, S.; Huang, Y.; Zheng, L.T.; Ye, N. Discovery of N-phenyl-1-(phenylsulfonamido)cyclopropane-1-carboxamide analogs as NLRP3 inflammasome inhibitors. Med. Chem. Res., 2021, 30(6), 1294-1308.
[http://dx.doi.org/10.1007/s00044-021-02740-7]
[123]
Narros-Fernández, P.; Chioua, M.; Petcu, S.A.; Diez-Iriepa, D.; Cerrada-Gálvez, L.; Decouty-Pérez, C.; Palomino-Antolín, A.; Ramos, E.; Farré-Alins, V.; López-Rodríguez, A.B.; Romero, A.; Marco-Contelles, J.; Egea, J. Synthesis and pharmacological evaluation of new N-sulfonylureas as NLRP3 inflammasome inhibitors: Identification of a hit compound to treat gout. J. Med. Chem., 2022, 65(8), 6250-6260.
[http://dx.doi.org/10.1021/acs.jmedchem.2c00149] [PMID: 35403430]
[124]
Harrison, D.; Bock, M.G.; Doedens, J.R.; Gabel, C.A.; Holloway, M.K.; Lewis, A.; Scanlon, J.; Sharpe, A.; Simpson, I.D.; Smolak, P.; Wishart, G.; Watt, A.P. Discovery and optimization of triazolopyrimidinone derivatives as selective NLRP3 inflammasome inhibitors. ACS Med. Chem. Lett., 2022, 13(8), 1321-1328.
[http://dx.doi.org/10.1021/acsmedchemlett.2c00242] [PMID: 35978696]
[125]
Ma, T.; Thiagarajah, J.R.; Yang, H.; Sonawane, N.D.; Folli, C.; Galietta, L.J.V.; Verkman, A.S. Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin–induced intestinal fluid secretion. J. Clin. Invest., 2002, 110(11), 1651-1658.
[http://dx.doi.org/10.1172/JCI0216112] [PMID: 12464670]
[126]
Jiang, H.; He, H.; Chen, Y.; Huang, W.; Cheng, J.; Ye, J.; Wang, A.; Tao, J.; Wang, C.; Liu, Q.; Jin, T.; Jiang, W.; Deng, X.; Zhou, R. Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders. J. Exp. Med., 2017, 214(11), 3219-3238.
[http://dx.doi.org/10.1084/jem.20171419] [PMID: 29021150]
[127]
Chen, Y.; He, H.; Jiang, H.; Li, L.; Hu, Z.; Huang, H.; Xu, Q.; Zhou, R.; Deng, X. Discovery and optimization of 4-oxo-2-thioxo-thiazolidinones as NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inhibitors. Bioorg. Med. Chem. Lett., 2020, 30(7), 127021.
[http://dx.doi.org/10.1016/j.bmcl.2020.127021] [PMID: 32057583]
[128]
Zuo, D.; Do, N.; Hwang, I.; Ann, J.; Yu, J.W.; Lee, J. Design and synthesis of an N-benzyl 5-(4-sulfamoylbenzylidene-2-thioxothiazolidin-4-one scaffold as a novel NLRP3 inflammasome inhibitor. Bioorg. Med. Chem. Lett., 2022, 65, 128693.
[http://dx.doi.org/10.1016/j.bmcl.2022.128693] [PMID: 35314328]
[129]
Liu, W.; Guo, W.; Wu, J.; Luo, Q.; Tao, F.; Gu, Y.; Shen, Y.; Li, J.; Tan, R.; Xu, Q.; Sun, Y. A novel benzo[d]imidazole derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of NLRP3 inflammasome. Biochem. Pharmacol., 2013, 85(10), 1504-1512.
[http://dx.doi.org/10.1016/j.bcp.2013.03.008] [PMID: 23506741]
[130]
Pan, L.; Hang, N.; Zhang, C.; Chen, Y.; Li, S.; Sun, Y.; Li, Z.; Meng, X. Synthesis and biological evaluation of novel benzimidazole derivatives and analogs targeting the NLRP3 inflammasome. Molecules, 2017, 22(2), 213.
[http://dx.doi.org/10.3390/molecules22020213] [PMID: 28146092]
[131]
Chen, H.; Chen, X.; Sun, P.; Wu, D.; Yue, H.; Pan, J.; Li, X.; Zhang, C.; Wu, X.; Hua, L.; Hu, W.; Yang, Z. Discovery of dronedarone and its analogues as NLRP3 inflammasome inhibitors with potent anti-inflammation activity. Bioorg. Med. Chem. Lett., 2021, 46, 128160.
[http://dx.doi.org/10.1016/j.bmcl.2021.128160] [PMID: 34062252]
[132]
Huang, Y.; Jiang, H.; Chen, Y.; Wang, X.; Yang, Y.; Tao, J.; Deng, X.; Liang, G.; Zhang, H.; Jiang, W.; Zhou, R. Tranilast directly targets NLRP 3 to treat inflammasome-driven diseases. EMBO Mol. Med., 2018, 10(4), e8689.
[http://dx.doi.org/10.15252/emmm.201708689] [PMID: 29531021]
[133]
Zhuang, T.; Li, S.; Yi, X.; Guo, S.; Wang, Y.; Chen, J.; Liu, L.; Jian, Z.; Gao, T.; Kang, P.; Li, C. Tranilast directly targets NLRP3 to protect melanocytes from keratinocyte-derived IL-1β under oxidative stress. Front. Cell Dev. Biol., 2020, 8, 588.
[http://dx.doi.org/10.3389/fcell.2020.00588] [PMID: 32754591]
[134]
Abdullaha, M.; Ali, M.; Kour, D.; Kumar, A.; Bharate, S.B. Discovery of benzo[cd]indol-2-one and benzylidene-thiazolidine-2,4-dione as new classes of NLRP3 inflammasome inhibitors via ER-β structure based virtual screening. Bioorg. Chem., 2020, 95, 103500.
[http://dx.doi.org/10.1016/j.bioorg.2019.103500] [PMID: 31869665]
[135]
Abdullaha, M.; Ali, M.; Kour, D.; Mudududdla, R.; Khajuria, P.; Kumar, A.; Bharate, S.B. 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 Pharmacol. Transl. Sci., 2021, 4(4), 1437-1448.
[http://dx.doi.org/10.1021/acsptsci.1c00126] [PMID: 34423275]
[136]
Sebastian-Valverde, M.; Wu, H.; Al Rahim, M.; Sanchez, R.; Kumar, K.; De Vita, R.J.; Pasinetti, G.M. Discovery and characterization of small-molecule inhibitors of NLRP3 and NLRC4 inflammasomes. J. Biol. Chem., 2021, 296, 100597.
[http://dx.doi.org/10.1016/j.jbc.2021.100597] [PMID: 33781745]
[137]
Dai, Z.; Chen, X.; An, L.; Li, C.; Zhao, N.; Yang, F.; You, S.; Hou, C.; Li, K.; Jiang, C.; You, Q.; Di, B.; Xu, L. Development of novel tetrahydroquinoline inhibitors of NLRP3 inflammasome for potential treatment of DSS-induced mouse colitis. J. Med. Chem., 2021, 64(1), 871-889.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01924] [PMID: 33332136]
[138]
Baldwin, A.G.; Rivers-Auty, J.; Daniels, M.J.D.; White, C.S.; Schwalbe, C.H.; Schilling, T.; Hammadi, H.; Jaiyong, P.; Spencer, N.G.; England, H.; Luheshi, N.M.; Kadirvel, M.; Lawrence, C.B.; Rothwell, N.J.; Harte, M.K.; Bryce, R.A.; Allan, S.M.; Eder, C.; Freeman, S.; Brough, D. Boron-based inhibitors of the NLRP3 inflammasome. Cell Chem. Biol., 2017, 24(11), 1321-1335.e5.
[http://dx.doi.org/10.1016/j.chembiol.2017.08.011] [PMID: 28943355]
[139]
Jiao, Y.; Nan, J.; Mu, B.; Zhang, Y.; Zhou, N.; Yang, S.; Zhang, S.; Lin, W.; Wang, F.; Xia, A.; Cao, Z.; Chen, P.; Pan, Z.; Lin, G.; Pan, S.; Bin, H.; Li, L.; Yang, S. Discovery of a novel and potent inhibitor with differential species-specific effects against NLRP3 and AIM2 inflammasome-dependent pyroptosis. Eur. J. Med. Chem., 2022, 232, 114194.
[http://dx.doi.org/10.1016/j.ejmech.2022.114194] [PMID: 35183871]
[140]
Abdullaha, M.; Mohammed, S.; Ali, M.; Kumar, A.; Vishwakarma, R.A.; Bharate, S.B. Discovery of quinazolin-4(3H)-ones as NLRP3 inflammasome inhibitors: Computational design, metal-free synthesis, and in vitro biological evaluation. J. Org. Chem., 2019, 84(9), 5129-5140.
[http://dx.doi.org/10.1021/acs.joc.9b00138] [PMID: 30896160]
[141]
Liao, K.C.; Sandall, C.F.; Carlson, D.A.; Ulke-Lemée, A.; Platnich, J.M.; Hughes, P.F.; Muruve, D.A.; Haystead, T.A.J.; MacDonald, J.A. Application of immobilized ATP to the study of NLRP inflammasomes. Arch. Biochem. Biophys., 2019, 670, 104-115.
[http://dx.doi.org/10.1016/j.abb.2018.12.031] [PMID: 30641048]
[142]
Gastaldi, S.; Boscaro, V.; Gianquinto, E.; Sandall, C.F.; Giorgis, M.; Marini, E.; Blua, F.; Gallicchio, M.; Spyrakis, F.; MacDonald, J.A.; Bertinaria, M. 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.
[http://dx.doi.org/10.3390/molecules26133975] [PMID: 34209843]
[143]
Haseeb, M.; Javaid, N.; Yasmeen, F.; Jeong, U.; Han, J.H.; Yoon, J.; Seo, J.Y.; Heo, J.K.; Shin, H.C.; Kim, M.S.; Kim, W.; Choi, S. Novel small-molecule inhibitor of NLRP3 inflammasome reverses cognitive impairment in an Alzheimer’s disease model. ACS Chem. Neurosci., 2022, 13(6), 818-833.
[http://dx.doi.org/10.1021/acschemneuro.1c00831] [PMID: 35196855]
[144]
Cocco, M.; Garella, D.; Di Stilo, A.; Borretto, E.; Stevanato, L.; Giorgis, M.; Marini, E.; Fantozzi, R.; Miglio, G.; Bertinaria, M. Electrophilic warhead-based design of compounds preventing NLRP3 inflammasome-dependent pyroptosis. J. Med. Chem., 2014, 57(24), 10366-10382.
[http://dx.doi.org/10.1021/jm501072b] [PMID: 25418070]
[145]
Cocco, M.; Miglio, G.; Giorgis, M.; Garella, D.; Marini, E.; Costale, A.; Regazzoni, L.; Vistoli, G.; Orioli, M.; Massulaha-Ahmed, R.; Détraz-Durieux, I.; Groslambert, M.; Py, B.F.; Bertinaria, M. Design, synthesis, and evaluation of acrylamide derivatives as direct NLRP3 inflammasome inhibitors. ChemMedChem, 2016, 11(16), 1790-1803.
[http://dx.doi.org/10.1002/cmdc.201600055] [PMID: 26990578]
[146]
Cocco, M.; Pellegrini, C.; Martínez-Banaclocha, H.; Giorgis, M.; Marini, E.; Costale, A.; Miglio, G.; Fornai, M.; Antonioli, L.; López-Castejón, G.; Tapia-Abellán, A.; Angosto, D.; Hafner-Bratkovič, I.; Regazzoni, L.; Blandizzi, C.; Pelegrín, P.; Bertinaria, M. Development of an acrylate derivative targeting the NLRP3 inflammasome for the treatment of inflammatory bowel disease. J. Med. Chem., 2017, 60(9), 3656-3671.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01624] [PMID: 28410442]
[147]
Juliana, C.; Fernandes-Alnemri, T.; Wu, J.; Datta, P.; Solorzano, L.; Yu, J.W.; Meng, R.; Quong, A.A.; Latz, E.; Scott, C.P.; Alnemri, E.S. Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome. J. Biol. Chem., 2010, 285(13), 9792-9802.
[http://dx.doi.org/10.1074/jbc.M109.082305] [PMID: 20093358]
[148]
Zhang, X.; Xu, A.; Ran, Y.; Wei, C.; Xie, F.; Wu, J. Design, synthesis and biological evaluation of phenyl vinyl sulfone based NLRP3 inflammasome inhibitors. Bioorg. Chem., 2022, 128, 106010.
[http://dx.doi.org/10.1016/j.bioorg.2022.106010] [PMID: 35914391]
[149]
Marchetti, C.; Swartzwelter, B.; Gamboni, F.; Neff, C.P.; Richter, K.; Azam, T.; Carta, S.; Tengesdal, I.; Nemkov, T.; D’Alessandro, A.; Henry, C.; Jones, G.S.; Goodrich, S.A.; St Laurent, J.P.; Jones, T.M.; Scribner, C.L.; Barrow, R.B.; Altman, R.D.; Skouras, D.B.; Gattorno, M.; Grau, V.; Janciauskiene, S.; Rubartelli, A.; Joosten, L.A.B.; Dinarello, C.A. OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proc. Natl. Acad. Sci., 2018, 115(7), E1530-E1539.
[http://dx.doi.org/10.1073/pnas.1716095115] [PMID: 29378952]
[150]
Lunding, L.P.; Skouras, D.B.; Vock, C.; Dinarello, C.A.; Wegmann, M. The NLRP3 inflammasome inhibitor, OLT1177®, ameliorates experimental allergic asthma in mice. Allergy, 2022, 77(3), 1035-1038.
[http://dx.doi.org/10.1111/all.15164] [PMID: 34716997]
[151]
Marchetti, C.; Swartzwelter, B.; Koenders, M.I.; Azam, T.; Tengesdal, I.W.; Powers, N.; de Graaf, D.M.; Dinarello, C.A.; Joosten, L.A.B. NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis. Arthritis Res. Ther., 2018, 20(1), 169.
[http://dx.doi.org/10.1186/s13075-018-1664-2] [PMID: 30075804]
[152]
Lonnemann, N.; Hosseini, S.; Marchetti, C.; Skouras, D.B.; Stefanoni, D.; D’Alessandro, A.; Dinarello, C.A.; Korte, M. The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci., 2020, 117(50), 32145-32154.
[http://dx.doi.org/10.1073/pnas.2009680117] [PMID: 33257576]
[153]
He, Y.; Varadarajan, S.; Muñoz-Planillo, R.; Burberry, A.; Nakamura, Y.; Núñez, G. 3,4-methylenedioxy-β-nitrostyrene inhibits NLRP3 inflammasome activation by blocking assembly of the inflammasome. J. Biol. Chem., 2014, 289(2), 1142-1150.
[http://dx.doi.org/10.1074/jbc.M113.515080] [PMID: 24265316]
[154]
Xiao, M.; Li, L.; Li, C.; Liu, L.; Yu, Y.; Ma, L. 3,4-Methylenedioxy-β-Nitrostyrene ameliorates experimental burn wound progression by inhibiting the NLRP3 inflammasome activation. Plast. Reconstr. Surg., 2016, 137(3), 566e-575e.
[http://dx.doi.org/10.1097/01.prs.0000479972.06934.83] [PMID: 26910701]
[155]
Chen, Y.; He, H.; Lin, B.; Chen, Y.; Deng, X.; Jiang, W.; Zhou, R. RRx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor. Cell. Mol. Immunol., 2021, 18(6), 1425-1436.
[http://dx.doi.org/10.1038/s41423-021-00683-y] [PMID: 33972740]
[156]
Jayabalan, N.; Oronsky, B.; Cabrales, P.; Reid, T.; Caroen, S.; Johnson, A.M.; Birch, N.A.; O’Sullivan, J.D.; Gordon, R. A review of RRx-001: A late-stage multi-indication inhibitor of NLRP3 activation and chronic inflammation. Drugs, 2023, 83(5), 389-402.
[http://dx.doi.org/10.1007/s40265-023-01838-z] [PMID: 36920652]
[157]
Shim, D.W.; Shin, W.Y.; Yu, S.H.; Kim, B.H.; Ye, S.K.; Koppula, S.; Won, H.S.; Kang, T.B.; Lee, K.H. BOT-4-one attenuates NLRP3 inflammasome activation: NLRP3 alkylation leading to the regulation of its ATPase activity and ubiquitination. Sci. Rep., 2017, 7(1), 15020.
[http://dx.doi.org/10.1038/s41598-017-15314-8] [PMID: 29118366]
[158]
Ou, Y.; Sun, P.; Wu, N.; Chen, H.; Wu, D.; Hu, W.; Yang, Z. Synthesis and biological evaluation of parthenolide derivatives with reduced toxicity as potential inhibitors of the NLRP3 inflammasome. Bioorg. Med. Chem. Lett., 2020, 30(17), 127399.
[http://dx.doi.org/10.1016/j.bmcl.2020.127399] [PMID: 32738997]
[159]
Chen, L.Z.; Zhang, X.X.; Liu, M.M.; Wu, J.; Ma, D.; Diao, L.Z.; Li, Q.; Huang, Y.S.; Zhang, R.; Ruan, B.F.; Liu, X.H. Discovery of novel pterostilbene-based derivatives as potent and orally active NLRP3 inflammasome inhibitors with inflammatory activity for colitis. J. Med. Chem., 2021, 64(18), 13633-13657.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01007] [PMID: 34506712]
[160]
Zhang, X.X.; Diao, L.Z.; Chen, L.Z.; Ma, D.; Wang, Y.M.; Jiang, H.; Ruan, B.F.; Liu, X.H. Discovery of 4-((E)-3,5-dimethoxy-2-((E)-2-nitrovinyl)styryl)aniline derivatives as potent and orally active NLRP3 inflammasome inhibitors for colitis. Eur. J. Med. Chem., 2022, 236, 114357.
[http://dx.doi.org/10.1016/j.ejmech.2022.114357] [PMID: 35428012]
[161]
Ruan, B.; Rong, M.; Ming, Z.; Wang, K.; Liu, X.; Deng, L.; Zhang, X.; Xu, K.; Shi, C.; Gao, T.; Liu, X.; Chen, L. Discovery of pterostilbene analogs as novel NLRP3 inflammasome inhibitors for potential treatment of DSS-induced colitis in mice. Bioorg. Chem., 2023, 133, 106429.
[http://dx.doi.org/10.1016/j.bioorg.2023.106429] [PMID: 36841048]
[162]
Zeng, Q.; Deng, H.; Li, Y.; Fan, T.; Liu, Y.; Tang, S.; Wei, W.; Liu, X.; Guo, X.; Jiang, J.; Wang, Y.; Song, D. Berberine directly targets the NEK7 protein to block the NEK7–NLRP3 interaction and exert anti-inflammatory activity. J. Med. Chem., 2021, 64(1), 768-781.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01743] [PMID: 33440945]
[163]
Li, J.; Sheng, H.; Wang, Y.; Lai, Z.; Wang, Y.; Cui, S. Scaffold hybrid of the natural product tanshinone I with piperidine for the discovery of a potent NLRP3 inflammasome inhibitor. J. Med. Chem., 2023, 66(4), 2946-2963.
[http://dx.doi.org/10.1021/acs.jmedchem.2c01967] [PMID: 36786612]
[164]
He, H.; Jiang, H.; Chen, Y.; Ye, J.; Wang, A.; Wang, C.; Liu, Q.; Liang, G.; Deng, X.; Jiang, W.; Zhou, R. Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity. Nat. Commun., 2018, 9(1), 2550.
[http://dx.doi.org/10.1038/s41467-018-04947-6] [PMID: 29959312]
[165]
Pang, L.; Liu, H.; Quan, H.; Sui, H.; Jia, Y. Development of novel oridonin analogs as specifically targeted NLRP3 inflammasome inhibitors for the treatment of dextran sulfate sodium-induced colitis. Eur. J. Med. Chem., 2023, 245(Pt 2), 114919.
[http://dx.doi.org/10.1016/j.ejmech.2022.114919] [PMID: 36399877]
[166]
Thapa, P.; Upadhyay, S.P.; Singh, V.; Boinpelly, V.C.; Zhou, J.; Johnson, D.K.; Gurung, P.; Lee, E.S.; Sharma, R.; Sharma, M. Chalcone: A potential scaffold for NLRP3 inflammasome inhibitors. Europ. J. Med. Chem. Rep., 2023, 7, 100100.
[http://dx.doi.org/10.1016/j.ejmcr.2022.100100] [PMID: 37033416]
[167]
Wang, K.; Lv, Q.; Miao, Y.; Qiao, S.; Dai, Y.; Wei, Z. Cardamonin, a natural flavone, alleviates inflammatory bowel disease by the inhibition of NLRP3 inflammasome activation via an AhR/Nrf2/NQO1 pathway. Biochem. Pharmacol., 2018, 155, 494-509.
[http://dx.doi.org/10.1016/j.bcp.2018.07.039] [PMID: 30071202]
[168]
Leu, W.J.; Chu, J.C.; Hsu, J.L.; Du, C.M.; Jiang, Y.H.; Hsu, L.C.; Huang, W.J.; Guh, J.H. Chalcones display anti-NLRP3 inflammasome activity in macrophages through inhibition of both priming and activation Steps-structure-activity-relationship and mechanism studies. Molecules, 2020, 25(24), 5960.
[http://dx.doi.org/10.3390/molecules25245960] [PMID: 33339319]
[169]
Tang, Y.L.; Zheng, X.; Qi, Y.; Pu, X.J.; Liu, B.; Zhang, X.; Li, X.S.; Xiao, W.L.; Wan, C.P.; Mao, Z.W. Synthesis and anti-inflammatory evaluation of new chalcone derivatives bearing bispiperazine linker as IL-1β inhibitors. Bioorg. Chem., 2020, 98, 103748.
[http://dx.doi.org/10.1016/j.bioorg.2020.103748] [PMID: 32179281]
[170]
Zhang, C.; Yue, H.; Sun, P.; Hua, L.; Liang, S.; Ou, Y.; Wu, D.; Wu, X.; Chen, H.; Hao, Y.; Hu, W.; Yang, Z. Discovery of chalcone analogues as novel NLRP3 inflammasome inhibitors with potent anti-inflammation activities. Eur. J. Med. Chem., 2021, 219, 113417.
[http://dx.doi.org/10.1016/j.ejmech.2021.113417] [PMID: 33845232]
[171]
Ma, X.; Zhao, M.; Tang, M.H.; Xue, L.L.; Zhang, R.J.; Liu, L.; Ni, H.F.; Cai, X.Y.; Kuang, S.; Hong, F.; Wang, L.; Chen, K.; Tang, H.; Li, Y.; Peng, A.H.; Yang, J.H.; Pei, H.Y.; Ye, H.Y.; Chen, L.J. Flavonoids with inhibitory effects on NLRP3 inflammasome activation from millettia velutina. J. Nat. Prod., 2020, 83(10), 2950-2959.
[http://dx.doi.org/10.1021/acs.jnatprod.0c00478] [PMID: 32989985]
[172]
Zhang, R.; Hong, F.; Zhao, M.; Cai, X.; Jiang, X.; Ye, N.; Su, K.; Li, N.; Tang, M.; Ma, X.; Ni, H.; Wang, L.; Wan, L.; Chen, L.; Wu, W.; Ye, H. New highly potent NLRP3 inhibitors: Furanochalcone velutone F analogues. ACS Med. Chem. Lett., 2022, 13(4), 560-569.
[http://dx.doi.org/10.1021/acsmedchemlett.1c00597] [PMID: 35450356]
[173]
Li, Q.; Feng, H.; Wang, H.; Wang, Y.; Mou, W.; Xu, G.; Zhang, P.; Li, R.; Shi, W.; Wang, Z.; Fang, Z.; Ren, L.; Wang, Y.; Lin, L.; Hou, X.; Dai, W.; Li, Z.; Wei, Z.; Liu, T.; Wang, J.; Guo, Y.; Li, P.; Zhao, X.; Zhan, X.; Xiao, X.; Bai, Z. Licochalcone B specifically inhibits the NLRP3 inflammasome by disrupting NEK7-NLRP3 interaction. EMBO Rep., 2022, 23(2), e53499.
[http://dx.doi.org/10.15252/embr.202153499] [PMID: 34882936]
[174]
Gong, Z.; Zhao, S.; Zhou, J.; Yan, J.; Wang, L.; Du, X.; Li, H.; Chen, Y.; Cai, W.; Wu, J. Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1β production. Mol. Immunol., 2018, 104, 11-19.
[http://dx.doi.org/10.1016/j.molimm.2018.09.004] [PMID: 30396035]
[175]
Zhang, X.; Hu, L.; Xu, S.; Ye, C.; Chen, A. Erianin: A direct NLRP3 inhibitor with remarkable anti-Inflammatory activity. Front. Immunol., 2021, 12, 739953.
[http://dx.doi.org/10.3389/fimmu.2021.739953] [PMID: 34745110]
[176]
Wang, H.; Lin, X.; Huang, G.; Zhou, R.; Lei, S.; Ren, J.; Zhang, K.; Feng, C.; Wu, Y.; Tang, W. Atranorin inhibits NLRP3 inflammasome activation by targeting ASC and protects NLRP3 inflammasome-driven diseases. Acta Pharmacol. Sin., 2023, 44(8), 1687-1700.
[http://dx.doi.org/10.1038/s41401-023-01054-1] [PMID: 36964308]
[177]
Xu, H.; Chen, J.; Chen, P.; Li, W.; Shao, J.; Hong, S.; Wang, Y.; Chen, L.; Luo, W.; Liang, G. Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases. Acta Pharm. Sin. B, 2023, 13(2), 678-693.
[http://dx.doi.org/10.1016/j.apsb.2022.09.014] [PMID: 36873170]
[178]
Xu, H.; Li, W.; Hong, S.; Shao, J.; Chen, J.; Chattipakorn, N.; Wu, D.; Luo, W.; Liang, G. Tabersonine, a natural NLRP3 inhibitor, suppresses inflammasome activation in macrophages and attenuate NLRP3-driven diseases in mice. Acta Pharmacol. Sin., 2022, 0, 1-10.
[PMID: 36627344]
[179]
Li, W.; Xu, H.; Shao, J.; Chen, J.; Lin, Y.; Zheng, Z.; Wang, Y.; Luo, W.; Liang, G. Discovery of alantolactone as a naturally occurring NLRP3 inhibitor to alleviate NLRP3‐driven inflammatory diseases in mice. Br. J. Pharmacol., 2023, 180(12), 1634-1647.
[http://dx.doi.org/10.1111/bph.16036] [PMID: 36668704]
[180]
Zhang, A.H.; Liu, W.; Jiang, N.; Xu, Q.; Tan, R.X. Spirodalesol, an NLRP3 inflammasome activation inhibitor. Org. Lett., 2016, 18(24), 6496-6499.
[http://dx.doi.org/10.1021/acs.orglett.6b03435] [PMID: 27978645]
[181]
Liu, W.; Yang, J.; Fang, S.; Jiao, C.; Gao, J.; Zhang, A.; Wu, T.; Tan, R.; Xu, Q.; Guo, W. Spirodalesol analog 8A inhibits NLRP3 inflammasome activation and attenuates inflammatory disease by directly targeting adaptor protein ASC. J. Biol. Chem., 2022, 298(12), 102696.
[http://dx.doi.org/10.1016/j.jbc.2022.102696] [PMID: 36379253]
[182]
Cui, W.; Chen, S.; Chi, Z.; Guo, X.; Zhang, X.; Zhong, Y.; Han, H.; Yao, K. Screening-based identification of xanthone as a novel NLRP3 inflammasome inhibitor via metabolic reprogramming. Clin. Transl. Med., 2021, 11(7), e496.
[http://dx.doi.org/10.1002/ctm2.496] [PMID: 34323410]
[183]
Ahmed, S.; Kwatra, M.; Ranjan Panda, S.; Murty, U.S.N.; Naidu, V.G.M. Andrographolide suppresses NLRP3 inflammasome activation in microglia through induction of parkin-mediated mitophagy in in-vitro and in-vivo models of Parkinson disease. Brain Behav. Immun., 2021, 91, 142-158.
[http://dx.doi.org/10.1016/j.bbi.2020.09.017] [PMID: 32971182]
[184]
González-Cofrade, L.; Oramas-Royo, S.; Cuadrado, I.; Amesty, Á.; Hortelano, S.; Estevez-Braun, A.; de las Heras, B. Dehydrohispanolone derivatives attenuate the inflammatory response through the modulation of inflammasome activation. J. Nat. Prod., 2020, 83(7), 2155-2164.
[http://dx.doi.org/10.1021/acs.jnatprod.0c00200] [PMID: 32584575]
[185]
Bi, D.W.; Xiong, F.; Cheng, B.; Zhou, Y.L.; Zeb, M.A.; Tang, P.; Pang, W.H.; Zhang, R.H.; Li, X.L.; Zhang, X.J.; Xiao, W.L. Callintegers A and B, unusual tricyclo [4.4.0.09,10]tetradecane clerodane diterpenoids from callicarpa integerrima with inhibitory effects on NLRP3 inflammasome activation. J. Nat. Prod., 2022, 85(11), 2675-2681.
[http://dx.doi.org/10.1021/acs.jnatprod.2c00568] [PMID: 36286259]
[186]
Pu, D.B.; Zhang, X.J.; Bi, D.W.; Gao, J.B.; Yang, Y.; Li, X.L.; Lin, J.; Li, X.N.; Zhang, R.H.; Xiao, W.L. Callicarpins, Two classes of rearranged ent-clerodane diterpenoids from callicarpa plants blocking NLRP3 inflammasome-induced pyroptosis. J. Nat. Prod., 2020, 83(7), 2191-2199.
[http://dx.doi.org/10.1021/acs.jnatprod.0c00288] [PMID: 32628479]
[187]
González-Cofrade, L.; P Green, J.; Cuadrado, I.; Amesty, Á.; Oramas-Royo, S.; David, Brough; Estévez-Braun, A.; Hortelano, S.; de Las Heras, B. Phenolic and quinone methide nor-triterpenes as selective NLRP3 inflammasome inhibitors. Bioorg. Chem., 2023, 132, 106362.
[http://dx.doi.org/10.1016/j.bioorg.2023.106362] [PMID: 36657273]
[188]
Chen, C.; Liu, X.; Gong, L.; Zhu, T.; Zhou, W.; Kong, L.; Luo, J. Identification of Tubocapsanolide A as a novel NLRP3 inhibitor for potential treatment of colitis. Biochem. Pharmacol., 2021, 190, 114645.
[http://dx.doi.org/10.1016/j.bcp.2021.114645] [PMID: 34090877]
[189]
Lin, G.; Li, N.; Li, D.; Chen, L.; Deng, H.; Wang, S.; Tang, J.; Ouyang, W. Carnosic acid inhibits NLRP3 inflammasome activation by targeting both priming and assembly steps. Int. Immunopharmacol., 2023, 116, 109819.
[http://dx.doi.org/10.1016/j.intimp.2023.109819] [PMID: 36738671]
[190]
Shi, J.; Xia, Y.; Wang, H.; Yi, Z.; Zhang, R.; Zhang, X. Piperlongumine is an NLRP3 inhibitor with anti-inflammatory activity. Front. Pharmacol., 2022, 12, 818326.
[http://dx.doi.org/10.3389/fphar.2021.818326] [PMID: 35095532]

Rights & Permissions Print Cite
Article Metrics
100
3
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy