Discovery of a novel and potent inhibitor with differential species-specific effects against NLRP3 and AIM2 inflammasome-dependent pyroptosis

Yan, Jiao; Nan, Jinshan; Mu, Bo; Zhang, Yun; Zhou, Nenghua; Yang, Shaoqiong; Zhang, Shanshan; Lin, Wen‐Chi; Wang, Falu; Xia, Anjie; Cao, Zhixing; Chen, Pei; Pan, Zhiling; Lin, Guifeng; Pan, Shulei; Bin, Huachao; Li, Linli; Yang, Shengyong

doi:10.1016/j.ejmech.2022.114194

Cited by 37 publications

(28 citation statements)

References 45 publications

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“…A recently identified novel compound 59 known as J114 was shown to interfere with NLRP3-ASC interaction and potently suppress ASC oligomerization during NLRP3 activation. Interestingly, the function of J114 exhibits species differences ( 126 ). Although research on this compound is still in the very beginning stage, J114 may be useful for further exploration of the exact modulatory mechanism of NLRP3 inflammasome.…”

Section: Potential Therapeutic Targets For the Nlrp3 Inflammasome In ...mentioning

confidence: 99%

Role of NLRP3 Inflammasome in Rheumatoid Arthritis

et al. 2022

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Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by multi-articular, symmetrical and invasive arthritis resulting from immune system abnormalities involving T and B lymphocytes. Although significant progress has been made in the understanding of RA pathogenesis, the underlying mechanisms are not fully understood. Recent studies suggest that NLRP3 inflammasome, a regulator of inflammation, might play an important role in the development of RA. There have been increasing clinical and pre-clinical evidence showing the treatment of NLRP3/IL-1β in inflammatory diseases. To provide a foundation for the development of therapeutic strategies, we will briefly summarize the roles of NLRP3 inflammasome in RA and explore its potential clinical treatment.

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Section: Potential Therapeutic Targets For the Nlrp3 Inflammasome In ...mentioning

confidence: 99%

Role of NLRP3 Inflammasome in Rheumatoid Arthritis

et al. 2022

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“…Interestingly, these indole compounds, such as 7 and 8 ( Figure 9 b), have some structural similarity to the recently published compound J114 ( Figure 9 c). The latter compound was reported to show both NLRP3 and AIM2 inhibition via inhibition of the interaction between ASC protein and the inflammasome [ 91 ]. Yan and coworkers [ 91 ] designed compound J114 ( IC 50 = 0.07 μM) by structure optimization of the hit compound 1 ( IC 50 = 3.1 μM) obtained from high-throughput screening ( Figure 9 c).…”

Section: Virtual Screening To Identify Possible Natural Product Scaff...mentioning

confidence: 99%

“…( b ) Structures of compounds 7 (ZINC ID: ZINC000217915463) and 8 (ZINC ID: ZINC000002616534). ( c ) The reported [ 91 ] hit compound 1 and the synthetic active NLRP3 inhibitor, J114 .…”

Section: Figurementioning

confidence: 99%

A Selective Review and Virtual Screening Analysis of Natural Product Inhibitors of the NLRP3 Inflammasome

2022

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The NLRP3 inflammasome is currently an exciting target for drug discovery due to its role in various inflammatory diseases; however, to date, no NLRP3 inhibitors have reached the clinic. Several studies have used natural products as hit compounds to facilitate the design of novel selective NLRP3 inhibitors. Here, we review selected natural products reported in the literature as NLRP3 inhibitors, with a particular focus on those targeting gout. To complement this survey, we also report a virtual screen of the ZINC20 natural product database, predicting favored chemical features that can aid in the design of novel small molecule NLRP3 inhibitors.

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“…However, these oligonucleotides might have off-target effects because they potentially also dampen Toll-like receptor 9 activation, as this receptor also recognizes DNA motifs. A subsequent study reported a compound that inhibits both NLRP3 and AIM2 in vitro 10 , but further studies are needed to test the in vivo specificity and efficacy of this drug. Drugs that interfere with the downstream inflammasome pathway, including caspase 1 (VX765), IL-1β (canakinumab) and IL-1 receptor (anakinra), have shown encouraging results in animal models and, to some extent, in clinical studies.…”

Section: Aim2 As a Target For Precision Medicinementioning

confidence: 99%